IL-18: The Forgotten Cytokine in Dengue Immunopathogenesis

Nanda, Josephine Diony; Ho, Tzong-Shiann; Satria, Rahmat Dani; Jhan, Ming-Kai; Wang, Yung-Ting; Lin, Chiou-Feng

doi:https://doi.org/10.1155/2021/8214656

Journal of Immunology Research

On this page

Abstract Introduction Conclusions Data Availability Conflicts of Interest Authors’ Contributions Acknowledgments References Copyright Related Articles

Special Issue

Immunopathogenesis of Neglected Tropical Diseases 2021

View this Special Issue

Review Article | Open Access

Volume 2021 | Article ID 8214656 | https://doi.org/10.1155/2021/8214656

IL-18: The Forgotten Cytokine in Dengue Immunopathogenesis

Josephine Diony Nanda,¹Tzong-Shiann Ho,^2,3Rahmat Dani Satria,^4,5,6Ming-Kai Jhan,^7,8Yung-Ting Wang,⁷and Chiou-Feng Lin^1,7,8

Academic Editor: Luiz Felipe Domingues Passero

Received01 Oct 2021

Revised25 Oct 2021

Accepted05 Nov 2021

Published19 Nov 2021

Abstract

Dengue fever is an infection by the dengue virus (DENV) transmitted by vector mosquitoes. It causes many infections in tropical and subtropical countries every year, thus posing a severe disease threat. Cytokine storms, one condition where many proinflammatory cytokines are mass-produced, might lead to cellular dysfunction in tissue/organ failures and often facilitate severe dengue disease in patients. Interleukin- (IL-) 18, similar to IL-1β, is a proinflammatory cytokine produced during inflammation following inflammasome activation. Inflammatory stimuli, including microbial infections, damage signals, and cytokines, all induce the production of IL-18. High serum IL-18 is remarkably correlated with severely ill dengue patients; however, its possible roles have been less explored. Based on the clinical and basic findings, this review discusses the potential immunopathogenic role of IL-18 when it participates in DENV infection and dengue disease progression based on existing findings and related past studies.

1. Introduction

Dengue disease is a primary Flaviviridae infection worldwide caused by the dengue virus (DENV) [1, 2]. DENV comprises four different serotypes (DENV1 to 4), with a wide range of genotypes and variants [3]. This myriad of DENV serotypes and variants are hypothesized to mediate its survival, together with increasing infectivity [4]. DENV infects humans as the primary host, transmitted via mosquitos mainly in tropical and subtropical areas [5]. Yearly, DENV is predicted to infect 100–400 million people worldwide [1]. Even though in 2021, the DENV infection incidence and mortality rate are reduced compared to 2020, the infection is still spread in many areas, increasing the health burden in this COVID-19 pandemic era [6]. Symptoms of the dengue diseases are widely varied. It could be shown as mild flu-like symptoms, mild dengue fever (MDF), to severe symptoms, the severe dengue diseases (SDDs,) in those who are infected. In MDF, the common symptom found is fever accompanied by one of the following: nausea, vomiting, rash, aches, and pains. Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are two types of severe dengue. In addition, multiple organ dysfunction and central nervous system (CNS) impairment are also involved in SDDs. Although rare, severe dengue can result in a variety of consequences, including excessive bleeding, organ damage, plasma leakage, and even death [1, 7–9].

2. Dengue Pathogenesis

Virus factors and host response majorly influence dengue severity. The variance in dengue serotype provides them numerous possibilities in causing severe DENV infection. As one of the oldest strains known, DENV-2 is more prevalent in causing severe dengue (DHF/DSS) and epidemics than other serotypes [4, 10, 11]. However, in several areas, DENV serotypes inducing severe infection started to shift to DENV-1, as reported in Singapore [12] and Indonesia [13]. Regarding the different subtypes of DENV, the American subtype is less likely to cause DHF/DSS than the Asian subtype. It might be facilitated by the higher replicability of the Asian subtype in the Aedes aegypti mosquitoes, enhancing their transmission [14, 15]. The DENV genetic variance also influences the intensity of the infection. For example, the difference in E-390 amino acid affects DENV virulence and survival, as it determines the virus’s ability to infect and replicate in monocyte-derived macrophages [16]. The sequence of the 3 untranslated region (UTR) also influences DENV virulence [17]. Other reports demonstrated that higher monocyte infectivity is associated with its ability to generate severe infections together with higher transmission [18].

More personalized factors influencing severe DENV infection, the host factors, are commonly found in secondary heterologous DENV infection, which causes antibody-dependent enhancement (ADE). This event is related to the inability of the previous dengue antibodies to neutralize the recent heterologous DENV infection, allowing easy access of the virus to infect the Fc-presenting cells. This will result in increased viral replication and severe infection [19–21]. Such cases can be observed in Peru, where homologous virus and American DENV-2 virus were neutralized far more efficiently by sera with DENV-1 antibody than Asian DENV-2 viruses [22]. Another situation found in Havana shows that the infection sequence also influences severity. In DENV-1 followed by DENV-3 (DENV-1/DENV-3), infection was linked to severe disease, but DENV-2/DENV-3 was linked to mild/asymptomatic infections. Interestingly, secondary infection also has higher genetic variability compared to the primary one. In DENV-1/DENV-3 secondary infection, changes in premembrane (PrM) and envelope (E) structural proteins might represent the DENV evolution to more potent strain overtimes [23]. This might explain the point regarding the infection incidence in serotype switch dengue epidemics [24].

3. Cytokine Response in DENV Infection

Cytokine storm, also called cytokine release syndrome (CRS), is an umbrella term describing several severe symptoms caused by systemic inflammatory syndromes encompassing an increase in blood cytokine levels and hyperactivation of immune cells. This condition may be caused by various pathogens, cancer, autoimmunity, and treatments that activate false alarms, leading to the hyperactivating immune system. Various factors affected cytokine storm incidences, such as genetics (improper inflammasome activation), an inappropriate or inadequate immune response involving activation of effector cells, an overwhelming viral burden, uncontrolled infection that causes prolonged immune stimulation, and the inability to resolve the immune response and revert to homeostasis. Negative feedback mechanisms that are supposed to prevent hyperinflammation and the overproduction of inflammatory cytokines and soluble mediators fail in each of these situations, leading to multiorgan damage [25]. Even though only a few reports regarding cytokine storms in flavivirus infections have been published, some infections, such as DENV [26], Zika virus (ZV) [27], West Nile virus (WNV) [28], Yellow fever virus (YFV) [29], and Japanese encephalitis virus (JEV) [30], are capable of causing cytokine disturbances that lead to poor patient outcomes.

In DENV infection, cytokine storms have been proposed to correlate with inflammasome activation [26, 31, 32]. DENV infected cells in vivo and in vitro are reported to have higher NLRP3-inflammasome activation via nonstructural (NS)2A and NS2B proteins induction [33], especially in mouse bone marrow-derived macrophages (BMDMs), endothelial cells, keratinocytes, platelets, dendritic cells (DCs), human peripheral blood mononuclear cells (PBMCs), and monocyte-differentiated macrophages (THP-1) [32]. Inflammasome activation also can be induced from reactive oxygen species (ROS) levels through extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and mitogen-activated protein kinases (MAPK) which found accumulated in DENV infected DCs. The intracellular ROS build-up has proven essential to influence the innate immune response in DENV clearance and promote mitochondrial apoptosis in infected DCs. Further, inflammasome activation will activate caspase and initiate pyroptosis, a lytic programmed cell death, in the cells. Simultaneously, caspase activation also cleavage the pro-IL-1β and pro-IL-18 to their active form, causing the inflammatory cascade to be activated and promoting further advances in dengue pathogenesis [34, 35].

A previous study reported an increase in cytokines, such as tumor necrosis factor- (TNF-) α, monocyte chemoattractant protein- (MCP-) 1 (CCL-2), regulated upon activation, normal T cell expressed and presumably secreted (RANTES) (CCL-5), interferon- (IFN-) γ, IFN-γ-induced protein- (IP-) 10 (CXCL-10), IL-4, IL-6, IL-8 (CXCL-8), IL-10, and granulocyte/macrophage colony-stimulating factor (GM-CSF) (CSF-2), in severe DENV infection [36–38]. Secondary infections mainly cause a cytokine storm in dengue due to the ADE effect, which results in overactivation of the immune system and excessive production of proinflammatory cytokines. However, this spurt of proinflammatory cytokines is not accompanied by proper degranulation functions, leading to ineffective eradication of infected cells [39]. Other evidence from the severe case febrile phase of dengue patients presented a decline in total CD4⁺ T, T helper (Th) 1, and Th17 cells in contrast to the convalescent phase [40], demonstrating why some patients move to recovery after the critical phase and others developed dysregulated cytokine production that led to fatal DENV infection followed by CRS progression.

4. The Biological Importance of IL-18

IL-18 is a cytokine previously known as IFN-γ-inducing factor (IGIF), firstly discovered in mice with endotoxin shock [41, 42]. Together with IL-1β and IL-33, IL-18 is also part of IL-1 family cytokines [43]. IL-18 is produced from immune cells, such as macrophages, Langerhans cells, DCs, and many nonimmune cells, such as osteoblasts, chondrocytes, endothelial cells, keratinocytes, and intestinal epithelial cells (Table 1) [44–51]. IL-18 and IL-1β are produced as inactive precursors activated via caspase cleavage, generally in an inflammasome-regulated manner, in the cytoplasm before being released into the bloodstream [52]. This activated form of IL-18 enhances adaptive immune activation by inducing IFN-γ production by T cells [53], Th1 polarization [54], cytotoxicity of both T cells and natural killer (NK) cells, and maturation of T, NK, and DCs [55, 56]. In addition, free IL-18 can cause innate immune macrophage activation by inducing polarization and inflammatory and cytokine secretion and can even cause macrophage activation syndrome (MAS) [57]. IL-1β itself is also known to induce several types of T cells development that take part in some inflammatory conditions and neutrophil recruitment to the infection site [58, 59].

IL-18 stimulation is mediated by IL-18 receptors (IL-18R), comprised of the α and β chains. The binding of IL-18 to IL-18R will relay the signals from myeloid differentiation primary response 88 (MyD88), a primary adapter protein for many TLR and IL-1R family members [60], to IL-1 receptor-associated kinase- (IRAK-) 1/4. Furthermore, IRAK-1/4 catalyzes the ubiquitination of TNF receptor-associated factor- (TRAF-) 6, leading to the activation of IκB kinase (IKK). This kinase will degrade IκB-NF-κB complexes in the cytoplasm, facilitating NF-κB nuclear translocation. This translocation will promote increased expression of various inflammatory cytokines [61], as summarized in Figure 1. Other inflammatory diseases have already proven the mitogen-activated protein kinase (MAPK) pathway involvement by IL-18R receptor activation; however, the role of this mechanism in flavivirus infection is still unknown.

Furthermore, the presence of other cytokines, such as IL-12 or IL-2, enhances the effect of IL-18 in immune cell activation. For example, together with IL-12, IL-18 promotes IFN-γ production from Th1 and B cells. Meanwhile, in NK cells, IL-18 alone is enough to cause IFN-γ production [53]. However, in an in vivo study, IL-12 and IL-18 were essential for maintaining NK cell activity and the Th1 response in bacterial stimulation [62]. In peripheral blood mononuclear cells (PBMCs) treated with IL-18 and IL-2, there was an increase in cytolytic activity, cell proliferation, and IFN-γ secretion. The isolated culture of NK cells showed higher proliferation and cytotoxicity activity in the presence of IL-18 and IL-2 compared to T cells [63]. In Th17 cells, IL-18 synergizes with IL-23 and amplifies IL-17 production via T cell receptor (TCR) activation [64]. The exciting part is that IL-18 not only induces Th1 cytokine production but is also capable of activating the humoral immune response via Th2 cytokine production. This phenomenon was first examined in mast cells and basophils cultured with IL-3, a factor required for hematopoietic proliferation and survival, exhibiting high IL-18Rα expression. Furthermore, stimulation with IL-18 and IL-3 induced massive production of IL-4 and IL-13. However, in the presence of IFN-γ and IL-12, the production of IL-4 and IL-13 from mast cells and basophils was highly suppressed [65]. Similar to basophils, treatment of NK and T cells harvested from IFN-γ knockout mice with IL-2 and IL-18 showed higher IL-13 mRNA expression than that of cells harvested from wild-type mice [66]. Also, IL-18, via MAPKs, including extracellular signal-regulated kinase (ERK) and p38 MAPK, and NF-κB activation, increases eosinophil survival and the production of IL-6, CXCL8, and CCL2 [67]. More discoveries from Yoshimoto et al. showed that along with IL-4, IL-18 promotes higher IgE production from CD4 T cells, and stimulation of TCR along with IL-18 boosts the differentiation of naïve CD4 T cells to IL-4-producing cells in vitro [68]. This complex interplay between cytokines suggests a broad role of IL-18 in determining the host cellular or humoral immune response.

5. IL-18 in DENV Infection

The first report about an IL-18 increase in a dengue patient clinical study was published in 2001, where the results from serum examination showed high IL-13 and IL-18 in the severe illness and late dengue disease phase (over 9 days from disease onset) patients [69]. A similar result was obtained from children’s cases in Venezuela. It was demonstrated that the IL-18 level was higher in dengue than in control. Moreover, the increase in IL-18 was not associated with NS1 or the infection type (primary or secondary) [70]. Our current report also showed a step ladder increase of IL-18 in severe DENV infection without and with comorbidity (hypertension and or diabetes) to the mild one. The correlation study also found a negative association between platelet and IL-18 level [71]. However, the induction of thrombocytopenia caused by aberrant expression of IL-18 and its possible pathogenic regulation needs further investigation.

The possible mechanism of the IL-18 increase in DENV infection is related to the presence of inflammatory macrophages. This was explained in an in vitro study using GM-CSF-induced macrophages (GM-Mϕs). In GM-Mϕs (CD14⁺) primary culture, DENV infection triggers NLRP3 inflammasome activation to cleavage pro-caspase 1 into caspase 1. Further, caspase-1 induces the maturation of pro-IL-1β and pro-IL-18, resulting in higher IL-1β and IL-18 production from GM-Mϕ [72]. The less mature form of macrophage, the monocyte, especially those expressing CD14⁺ or CD16⁺ markers, also secretes IL-18 which causes T-cell activation also IFN-γ secretion. However, this IFN-γ production is independent of monocyte presence [73].

IFN-γ producing NK cells are also being activated by DENV-induced IL-18 presence. During this event, the less mature NK cells will proliferate and prime to the skin to invade DENV [74]. Apart from those cells, activation of mucosal-associated invariant T (MAIT) cells was also reported following DENV infection. This activation was independent of TCR for cytokine release or Granzyme B upregulation, but it is dependent on IL-18 or in combination with IL-12, IL-15, and/or IFN-α/β. However, IL-18 levels and MAIT cell activation are linked to infection severity [75]. This peaked increase of IL-18 level might represent the severe patient condition where the inflammation is high. Despite the high level of inflammation, it is not always in line with the ability to eliminate the pathogens, risking it for producing a more severe cytokine response or CRS. In summary, according to the current studies related to DENV-induced IL-18, the possible effects of IL-18 on DENV infection, including cytokine storm, CRS/MAS, antiviral defense, and immune clearance, are summarized in Figure 2.

6. Potential Role of IL-18 in Flavivirus Infection and Other Diseases

Although the significance of IL-18 in aiding dengue illness progression is unknown, it has been observed that IL-18 production is changed in metabolic syndromes [76, 77], hypertension [78], diabetic patients [79], cardiovascular disorders [80], atherosclerosis [80, 81], and also several flavivirus infections such as JEV [82], tick-borne encephalitis virus (TBEV) [83], and ZV infection [84, 85]. This increase implies that the presence of IL-18 might play a role as either a protective or pathological cytokine to the host. The CSF of TBEV patients contains several proinflammatory cytokines, including IL-18, and it has a higher concentration of IP-10 (CXCL10), a T cell chemoattractant, than serum [86]. Furthermore, IL-18 is known to induce IFN-γ secretion from NK cells, despite suppressing NK cell function in TBEV infection [83]. In ZV infection, an increase in IL-18 levels is also found in pregnant women with fetal development anomalies and infants with CNS deformities [84]. In an in vivo model of JEV-infected mice, the expression of IL-1β and IL-18 was increased in the brain. When these cytokines are used to treat human microglia (CHME3) and astroglial (SVG) cell lines, increased secretion of proinflammatory cytokines is observed [82]. In contrast, in vitro WNV infection modeling does not show any increase in IL-18 production from infected human primary DCs [87] or the transformed human neuroblastoma cell line SK-N-SH [88]. Although there was no increase in IL-18 in response to WNV infection, the NOD-, LRR-, and pyrin domain-containing protein- (NLRP-) 3 inflammasome and IL-1β play vital roles in WNT-infected mouse survival. An increased viral load was also found in NLRP3-deficient mice [89]. In Table 2, we summarized IL-18 production in all flavivirus infections and its possible regulation of immune responses. However, most studies are clinical association studies and animal models of infection. No mechanistic investigations have been published.

In the atopic dermatitis mouse model, the knockout of IL-18 reduces skin lesion formation [90]. It means the involvement in Th2-cytokine production and major cytokine plays a role in an allergy reaction. Previously, it has been reported that in DHF, there are shifts of cytokine from Th1 to Th2 type [91], implying its possible role in causing severe dengue progression. Also, IL-18 is one of the cytokines that induce DM patient progression to nephropathy [92]. In chronic obstructive pulmonary disease (COPD) patients, smokers and the end stage of COPD has higher serum level of IL-18 in those who were not smoking and lower stage [93]. Compared to stable, asymptomatic plaques in atherosclerotic patients, unstable plaques had considerably more significant levels of IL-18 mRNA [94]. These two roles of IL-18 in COPD and atherosclerotic patients might indicate the role of IL-18 as a proinflammatory cytokine, worsening the condition of the disease. The IL-18 role in cancer is explained as a dual-edge sword, as its secretion of IFN-γ acts as an antitumor mechanism. However, in some cancer polymorphisms, IL-18 correlated with protumoral effects and upregulated VEGF and SD-44 that facilitate metastasis [95]. In triple-negative breast cancer, tumor-derived IL-18 has also been reported to increase PD-1 expression on immunosuppressive NK cells [96], facilitating the immune evasion of the cancer cells. The possible regulation of IL-18 in nonviral human diseases is summarized in Table 3.

7. Conclusions

The role of IL-18 in immunomodulating the antiviral response has been studied not only in DENV but also in other diseases. However, in the specific circumstances of high viral burden that cause a lot of infected cell pyroptosis, high levels of IL-18 were secreted, promoting immune overactivation and contributing to the further immunopathogenesis of DENV infection. Together with this understanding, suppressing the activity or production of IL-18 in severely infected patients might prevent the immune overactivation, thus avoiding more severe progression of the disease.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that there is no conflict of interest.

Authors’ Contributions

J.-D.N., T.-S.H., R.-D.S., M.-K.J., Y.-T.W., and C.-F.L. designed the concept of the project and wrote the manuscript. All authors reviewed and approved the manuscript.

Acknowledgments

This work was supported by the Ministry of Science and Technology (MOST109-2327-B-006-010, 110-2327-B-006-005, and 110-2320-B-038-064-MY3), Taiwan.

References

WHO, “Dengue and severe dengue: World Health Organization,” 2021, https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue.
View at: Google Scholar
C. A. Daep, J. L. Muñoz-Jordán, and E. A. Eugenin, “Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus,” Journal of Neurovirology, vol. 20, no. 6, pp. 539–560, 2014.
View at: Publisher Site | Google Scholar
O. M. Ekwudu, L. Marquart, L. Webb et al., “Effect of serotype and strain diversity on dengue virus replication in Australian mosquito vectors,” Pathogens, vol. 9, no. 8, p. 668, 2020.
View at: Publisher Site | Google Scholar
E. C. Holmes and S. S. Twiddy, “The origin, emergence and evolutionary genetics of dengue virus,” Infection, Genetics and Evolution, vol. 3, no. 1, pp. 19–28, 2003.
View at: Publisher Site | Google Scholar
S. Bhatt, P. W. Gething, O. J. Brady et al., “The global distribution and burden of dengue,” Nature, vol. 496, no. 7446, pp. 504–507, 2013.
View at: Publisher Site | Google Scholar
WHO, Dengue Situation Update Number 629, 2021.
World Health Organization ROfS-EA, Comprehensive Guideline for Prevention and Control of Dengue and Dengue Haemorrhagic Fever. Revised and Expanded Edition, WHO Regional Office for South-East Asia, 2011.
S. Kalayanarooj, “Clinical manifestations and management of dengue/DHF/DSS,” Trop Med Health, vol. 39, 4 Suppl, pp. 83–87, 2011.
View at: Publisher Site | Google Scholar
CDC, “Dengue 2021,” September 2021, https://www.cdc.gov/dengue/symptoms/index.html.
View at: Google Scholar
C. R. Vicente, K.-H. Herbinger, G. Fröschl, C. Malta Romano, A. de Souza Areias Cabidelle, and C. Cerutti Junior, “Serotype influences on dengue severity: a cross-sectional study on 485 confirmed dengue cases in Vitória, Brazil,” BMC Infectious Diseases, vol. 16, no. 1, p. 320, 2016.
View at: Publisher Site | Google Scholar
S. P. Tseng, C. H. Yen, K. Chang et al., “Severe dengue fever outbreak in Taiwan,” The American Journal of Tropical Medicine and Hygiene, vol. 94, no. 1, pp. 193–197, 2016.
View at: Publisher Site | Google Scholar
C.-F. Yung, K.-S. Lee, T.-L. Thein et al., “Dengue serotype-specific differences in clinical manifestation, laboratory parameters and risk of severe disease in adults, Singapore,” The American Journal of Tropical Medicine and Hygiene, vol. 92, no. 5, pp. 999–1005, 2015.
View at: Publisher Site | Google Scholar
S. N. N. Tatura, D. Denis, M. S. Santoso et al., “Outbreak of severe dengue associated with DENV-3 in the city of Manado, North Sulawesi, Indonesia,” International Journal of Infectious Diseases, vol. 106, pp. 185–196, 2021.
View at: Publisher Site | Google Scholar
K. C. Leitmeyer, D. W. Vaughn, D. M. Watts, R. Salas, and I. Villalobos, “Dengue virus structural differences that correlate with pathogenesis,” Journal of Virology, vol. 73, no. 6, pp. 4738–4747, 1999.
View at: Publisher Site | Google Scholar
P. M. Armstrong and R. Rico-Hesse, “Differential susceptibility of Aedes aegypti to infection by the American and Southeast Asian genotypes of dengue type 2 virus,” Vector Borne and Zoonotic Diseases, vol. 1, no. 2, pp. 159–168, 2001.
View at: Publisher Site | Google Scholar
M. J. Pryor, J. M. Carr, H. Hocking, A. D. Davidson, P. Li, and P. J. Wright, “Replication of dengue virus type 2 in human monocyte-derived macrophages: comparisons of isolates and recombinant viruses with substitutions at amino acid 390 in the envelope glycoprotein,” The American Journal of Tropical Medicine and Hygiene, vol. 65, no. 5, pp. 427–434, 2001.
View at: Publisher Site | Google Scholar
V. Proutski, T. S. Gritsun, E. A. Gould, and E. C. Holmes, “Biological consequences of deletions within the 3-untranslated region of flaviviruses may be due to rearrangements of RNA secondary structure,” Virus Research, vol. 64, no. 2, pp. 107–123, 1999.
View at: Publisher Site | Google Scholar
S. Kliks, “Antibody-enhanced infection of monocytes as the pathogenetic mechanism for severe dengue illness,” AIDS Research and Human Retroviruses, vol. 6, no. 8, pp. 993–998, 1990.
View at: Publisher Site | Google Scholar
A. P. Goncalvez, R. E. Engle, M. St Claire, R. H. Purcell, and C. J. Lai, “Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 22, pp. 9422–9427, 2007.
View at: Publisher Site | Google Scholar
A. Taylor, S. S. Foo, R. Bruzzone, L. V. Dinh, N. J. King, and S. Mahalingam, “Fc receptors in antibody-dependent enhancement of viral infections,” Immunological Reviews, vol. 268, no. 1, pp. 340–364, 2015.
View at: Publisher Site | Google Scholar
D. W. Vaughn, S. Green, S. Kalayanarooj et al., “Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity,” The Journal of Infectious Diseases, vol. 181, no. 1, pp. 2–9, 2000.
View at: Publisher Site | Google Scholar
T. J. Kochel, D. M. Watts, S. B. Halstead et al., “Effect of dengue-1 antibodies on American dengue-2 viral infection and dengue haemorrhagic fever,” The Lancet, vol. 360, no. 9329, pp. 310–312, 2002.
View at: Publisher Site | Google Scholar
R. Rodriguez-Roche, H. Blanc, A. V. Bordería et al., “Increasing clinical severity during a dengue virus type 3 Cuban epidemic: deep sequencing of evolving viral populations,” Journal of Virology, vol. 90, no. 9, pp. 4320–4333, 2016.
View at: Publisher Site | Google Scholar
H. C. Hapuarachchi, C. Koo, J. Rajarethinam et al., “Epidemic resurgence of dengue fever in Singapore in 2013-2014: a virological and entomological perspective,” BMC Infectious Diseases, vol. 16, no. 1, p. 300, 2016.
View at: Publisher Site | Google Scholar
D. C. Fajgenbaum and C. H. June, “Cytokine Storm,” New England Journal of Medicine, vol. 383, no. 23, pp. 2255–2273, 2020.
View at: Publisher Site | Google Scholar
A. Srikiatkhachorn, A. Mathew, and A. L. Rothman, “Immune-mediated cytokine storm and its role in severe dengue,” Seminars in Immunopathology, vol. 39, no. 5, pp. 563–574, 2017.
View at: Publisher Site | Google Scholar
C. Maucourant, G. A. N. Queiroz, A. Samri, M. F. R. Grassi, H. Yssel, and V. Vieillard, “Zika virus in the eye of the cytokine storm,” European Cytokine Network, vol. 30, no. 3, pp. 74–81, 2019.
View at: Publisher Site | Google Scholar
A. A. Leis, M. F. Grill, B. P. Goodman et al., “Tumor necrosis factor-alpha signaling may contribute to chronic West Nile virus post-infectious proinflammatory state,” Frontiers in Medicine, vol. 7, no. 164, 2020.
View at: Publisher Site | Google Scholar
J. ter Meulen, M. Sakho, K. Koulemou et al., “Activation of the cytokine network and unfavorable outcome in patients with yellow fever,” The Journal of Infectious Diseases, vol. 190, no. 10, pp. 1821–1827, 2004.
View at: Publisher Site | Google Scholar
P. M. Winter, N. M. Dung, H. T. Loan et al., “Proinflammatory cytokines and chemokines in humans with Japanese encephalitis,” The Journal of Infectious Diseases, vol. 190, no. 9, pp. 1618–1626, 2004.
View at: Publisher Site | Google Scholar
T. H. Nguyen, T. H. Nguyen, T. T. Vu et al., “Corticosteroids for dengue - why don’t they work?” PLoS Neglected Tropical Diseases, vol. 7, no. 12, article e2592, 2013.
View at: Publisher Site | Google Scholar
G. Shrivastava, P. C. Valenzuela Leon, and E. Calvo, “Inflammasome fuels dengue severity,” Frontiers in Cellular and Infection Microbiology, vol. 10, p. 489, 2020.
View at: Publisher Site | Google Scholar
G. Shrivastava, G. Visoso-Carvajal, J. Garcia-Cordero et al., “Dengue virus serotype 2 and its non-structural proteins 2A and 2B activate NLRP3 inflammasome,” Frontiers in Immunology, vol. 11, p. 352, 2020.
View at: Publisher Site | Google Scholar
A. Harijith, D. L. Ebenezer, and V. Natarajan, “Reactive oxygen species at the crossroads of inflammasome and inflammation,” Frontiers in Physiology, vol. 5, p. 352, 2014.
View at: Publisher Site | Google Scholar
D. Olagnier, S. Peri, C. Steel et al., “Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells,” PLoS Pathogens, vol. 10, no. 12, article e1004566-e, 2014.
View at: Publisher Site | Google Scholar
W. H. Wang, C. Y. Lin, K. Chang et al., “A clinical and epidemiological survey of the largest dengue outbreak in Southern Taiwan in 2015,” International Journal of Infectious Diseases, vol. 88, pp. 88–99, 2019.
View at: Publisher Site | Google Scholar
L. Cui, Y. H. Lee, T. L. Thein et al., “Serum metabolomics reveals serotonin as a predictor of severe dengue in the early phase of dengue fever,” PLoS Neglected Tropical Diseases, vol. 10, no. 4, article e0004607, 2016.
View at: Publisher Site | Google Scholar
G. Patra, S. Mallik, B. Saha, and S. Mukhopadhyay, “Assessment of chemokine and cytokine signatures in patients with dengue infection: a hospital-based study in Kolkata, India,” Acta Tropica, vol. 190, pp. 73–79, 2019.
View at: Publisher Site | Google Scholar
D. Kuczera, J. P. Assolini, F. Tomiotto-Pellissier, W. R. Pavanelli, and G. F. Silveira, “Highlights for dengue immunopathogenesis: antibody-dependent enhancement, cytokine storm, and beyond,” Journal of Interferon & Cytokine Research, vol. 38, no. 2, pp. 69–80, 2018.
View at: Publisher Site | Google Scholar
D. H. Manh, L. N. Weiss, N. V. Thuong et al., “Kinetics of CD4+ T helper and CD8+ effector T cell responses in acute dengue patients,” Frontiers in Immunology, vol. 11, no. 1980, 2020.
View at: Publisher Site | Google Scholar
H. Okamura, H. Tsutsui, T. Komatsu et al., “Cloning of a new cytokine that induces IFN-γ production by T cells,” Nature, vol. 378, no. 6552, pp. 88–91, 1995.
View at: Publisher Site | Google Scholar
K. Nakamura, H. Okamura, K. Nagata, T. Komatsu, and T. Tamura, “Purification of a factor which provides a costimulatory signal for gamma interferon production,” Infection and Immunity, vol. 61, no. 1, pp. 64–70, 1993.
View at: Publisher Site | Google Scholar
J. K. Fields, S. Günther, and E. J. Sundberg, “Structural basis of IL-1 family cytokine signaling,” Frontiers in Immunology, vol. 10, no. 1412, 2019.
View at: Publisher Site | Google Scholar
H. P. Carroll, V. Paunović, and M. Gadina, “Signalling, inflammation and arthritis: crossed signals: the role of interleukin-15 and -18 in autoimmunity,” Rheumatology, vol. 47, no. 9, pp. 1269–1277, 2008.
View at: Publisher Site | Google Scholar
K. Yasuda, K. Nakanishi, and H. Tsutsui, “Interleukin-18 in health and disease,” International Journal of Molecular Sciences, vol. 20, no. 3, p. 649, 2019.
View at: Publisher Site | Google Scholar
N. Udagawa, N. J. Horwood, J. Elliott et al., “Interleukin-18 (interferon-γ–inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-γ to inhibit osteoclast formation,” The Journal of Experimental Medicine, vol. 185, no. 6, pp. 1005–1012, 1997.
View at: Publisher Site | Google Scholar
H. Koizumi, K. C. Sato-Matsumura, H. Nakamura et al., “Distribution of IL-18 and IL-18 receptor in human skin: various forms of IL-18 are produced in keratinocytes,” Archives of Dermatological Research, vol. 293, no. 7, pp. 325–333, 2001.
View at: Publisher Site | Google Scholar
P. Holmkvist, K. Roepstorff, H. Uronen-Hansson et al., “A major population of mucosal memory CD4⁺ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality,” Mucosal Immunology, vol. 8, no. 3, pp. 545–558, 2015.
View at: Publisher Site | Google Scholar
S. Stoll, H. Jonuleit, E. Schmitt et al., “Production of functional IL-18 by different subtypes of murine and human dendritic cells (DC): DC-derived IL-18 enhances IL-12-dependent Th1 development,” European Journal of Immunology, vol. 28, no. 10, pp. 3231–3239, 1998.
View at: Publisher Site | Google Scholar
P. Brossart, F. Grünebach, G. Stuhler et al., “Generation of functional human dendritic cells from adherent peripheral blood monocytes by CD40 ligation in the absence of granulocyte-macrophage colony-stimulating factor,” Blood, vol. 92, no. 11, pp. 4238–4247, 1998.
View at: Publisher Site | Google Scholar
A. Grandjean-Laquerriere, P. Laquerriere, D. Laurent-Maquin, M. Guenounou, and T. M. Phillips, “The effect of the physical characteristics of hydroxyapatite particles on human monocytes IL-18 production in vitro,” Biomaterials, vol. 25, no. 28, pp. 5921–5927, 2004.
View at: Publisher Site | Google Scholar
Y. Gu, K. Kuida, H. Tsutsui et al., “Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme,” Science, vol. 275, no. 5297, pp. 206–209, 1997.
View at: Publisher Site | Google Scholar
T. Yoshimoto, K. Takeda, T. Tanaka et al., “IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-γ production,” The Journal of Immunology, vol. 161, no. 7, p. 3400, 1998.
View at: Google Scholar
K. Kohno, J. Kataoka, T. Ohtsuki et al., “IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12,” The Journal of Immunology, vol. 158, no. 4, pp. 1541–1550, 1997.
View at: Google Scholar
C. A. Dinarello and G. Fantuzzi, “Interleukin-18 and host defense against infection,” The Journal of Infectious Diseases, vol. 187, Suppl 2, pp. S370–S384, 2003.
View at: Publisher Site | Google Scholar
J. Li, M. Lamine Mbow, L. Sun et al., “Induction of dendritic cell maturation by IL-18,” Cellular Immunology, vol. 227, no. 2, pp. 103–108, 2004.
View at: Publisher Site | Google Scholar
E. S. Weiss, C. Girard-Guyonvarc’h, D. Holzinger et al., “Interleukin-18 diagnostically distinguishes and pathogenically promotes human and murine macrophage activation syndrome,” Blood, vol. 131, no. 13, pp. 1442–1455, 2018.
View at: Publisher Site | Google Scholar
V. Santarlasci, L. Cosmi, L. Maggi, F. Liotta, and F. Annunziato, “IL-1 and T helper immune responses,” Frontiers in Immunology, vol. 4, no. 182, 2013.
View at: Publisher Site | Google Scholar
J. Niu, S. Wu, M. Chen et al., “Hyperactivation of the NLRP3 inflammasome protects mice against influenza A virus infection via IL-1β mediated neutrophil recruitment,” Cytokine, vol. 120, pp. 115–124, 2019.
View at: Publisher Site | Google Scholar
A. C. Oliveira, J. F. Gomes-Neto, C. D. Barbosa et al., “Crucial role for T cell-intrinsic IL-18R-MyD88 signaling in cognate immune response to intracellular parasite infection,” eLife, vol. 6, 2017.
View at: Publisher Site | Google Scholar
N. Tsutsumi, T. Kimura, K. Arita et al., “The structural basis for receptor recognition of human interleukin-18,” Nature Communications, vol. 5, no. 1, p. 5340, 2014.
View at: Publisher Site | Google Scholar
K. Takeda, H. Tsutsui, T. Yoshimoto et al., “Defective NK cell activity and Th1 response in IL-18-deficient mice,” Immunity, vol. 8, no. 3, pp. 383–390, 1998.
View at: Publisher Site | Google Scholar
Y.-I. Son, R. M. Dallal, R. B. Mailliard, S. Egawa, Z. L. Jonak, and M. T. Lotze, “Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-gamma production, and expansion of natural killer cells,” Cancer Research, vol. 61, no. 3, pp. 884–888, 2001.
View at: Google Scholar
L. E. Harrington, P. R. Mangan, and C. T. Weaver, “Expanding the effector CD4 T-cell repertoire: the Th17 lineage,” Current Opinion in Immunology, vol. 18, no. 3, pp. 349–356, 2006.
View at: Publisher Site | Google Scholar
T. Yoshimoto, H. Tsutsui, K. Tominaga et al., “IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 24, pp. 13962–13966, 1999.
View at: Publisher Site | Google Scholar
T. Hoshino, R. H. Wiltrout, and H. A. Young, “IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response,” The Journal of Immunology, vol. 162, no. 9, pp. 5070–5077, 1999.
View at: Google Scholar
J. Y. S. Chow, C. K. Wong, P. F. Y. Cheung, and C. W. K. Lam, “Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33: implications for allergic inflammation,” Cellular & Molecular Immunology, vol. 7, no. 1, pp. 26–34, 2010.
View at: Publisher Site | Google Scholar
T. Yoshimoto, H. Mizutani, H. Tsutsui, and N. Noben-Trauth, “IL-18 induction of IgE: dependence on CD4⁺ T cells, IL-4 and STAT6,” Nature Immunology, vol. 1, no. 2, pp. 132–137, 2000.
View at: Publisher Site | Google Scholar
A. S. Mustafa, E. A. Elbishbishi, R. Agarwal, and U. C. Chaturvedi, “Elevated levels of interleukin-13 and IL-18 in patients with dengue hemorrhagic fever,” FEMS Immunology and Medical Microbiology, vol. 30, no. 3, pp. 229–233, 2001.
View at: Publisher Site | Google Scholar
N. Valero, J. Mosquera, M. Torres et al., “Increased serum ferritin and interleukin-18 levels in children with dengue,” Brazilian Journal of Microbiology, vol. 50, no. 3, pp. 649–656, 2019.
View at: Publisher Site | Google Scholar
J. D. Nanda, C.-J. Jung, R. D. Satria et al., “Serum IL-18 Is a Potential Biomarker for Predicting Severe Dengue Disease Progression,” Journal of Immunology Research., vol. 2021, Article ID 7652569, pp. 1–15, 2021.
View at: Publisher Site | Google Scholar
M. F. Wu, S. T. Chen, A. H. Yang et al., “CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages,” Blood, vol. 121, no. 1, pp. 95–106, 2013.
View at: Publisher Site | Google Scholar
C. Y. Tsai, K. H. Liong, M. G. Gunalan et al., “Type I IFNs and IL-18 regulate the antiviral response of primary human γδ T cells against dendritic cells infected with dengue virus,” Journal of Immunology, vol. 194, no. 8, pp. 3890–3900, 2015.
View at: Publisher Site | Google Scholar
C. L. Zimmer, M. Cornillet, C. Solà-Riera et al., “NK cells are activated and primed for skin-homing during acute dengue virus infection in humans,” Nature Communications, vol. 10, no. 1, p. 3897, 2019.
View at: Publisher Site | Google Scholar
STOP-HCV consortium, B. van Wilgenburg, I. Scherwitzl et al., “MAIT cells are activated during human viral infections,” Nature Communications, vol. 7, no. 1, article 11653, 2016.
View at: Publisher Site | Google Scholar
J. Hung, B. M. McQuillan, C. M. L. Chapman, P. L. Thompson, and J. P. Beilby, “Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 6, pp. 1268–1273, 2005.
View at: Publisher Site | Google Scholar
M. Trøseid, I. Seljeflot, and H. Arnesen, “The role of interleukin-18 in the metabolic syndrome,” Cardiovascular Diabetology, vol. 9, no. 1, p. 11, 2010.
View at: Publisher Site | Google Scholar
S. W. Rabkin, “The role of interleukin 18 in the pathogenesis of hypertension-induced vascular disease,” Nature Clinical Practice. Cardiovascular Medicine, vol. 6, no. 3, pp. 192–199, 2009.
View at: Publisher Site | Google Scholar
E. Zaharieva, Z. Kamenov, T. Velikova, A. Tsakova, Y. El-Darawish, and H. Okamura, “Interleukin-18 serum level is elevated in type 2 diabetes and latent autoimmune diabetes,” Endocrine Connections, vol. 7, no. 1, pp. 179–185, 2018.
View at: Publisher Site | Google Scholar
O. Bhat and V. Dhawan, “Role of IL-18 and its signaling in atherosclerosis,” Inflammation and Cell Signaling, vol. 2, 2015.
View at: Google Scholar
Z. Mallat, A. Corbaz, A. Scoazec et al., “Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability,” Circulation, vol. 104, no. 14, pp. 1598–1603, 2001.
View at: Publisher Site | Google Scholar
S. Das, M. K. Mishra, J. Ghosh, and A. Basu, “Japanese Encephalitis Virus infection induces IL-18 and IL-1β in microglia and astrocytes: correlation with in vitro cytokine responsiveness of glial cells and subsequent neuronal death,” Journal of Neuroimmunology, vol. 195, no. 1-2, pp. 60–72, 2008.
View at: Publisher Site | Google Scholar
K. Blom, M. Braun, J. Pakalniene et al., “NK cell responses to human tick-borne encephalitis virus infection,” Journal of Immunology, vol. 197, no. 7, pp. 2762–2771, 2016.
View at: Publisher Site | Google Scholar
Y. W. Kam, J. A. Leite, F. M. Lum et al., “Specific biomarkers associated with neurological complications and congenital central nervous system abnormalities from Zika virus-infected patients in Brazil,” The Journal of Infectious Diseases, vol. 216, no. 2, pp. 172–181, 2017.
View at: Publisher Site | Google Scholar
S. F. Khaiboullina, T. Uppal, R. Sarkar, A. Gorzalski, S. St Jeor, and S. C. Verma, “ZIKV infection regulates inflammasomes pathway for replication in monocytes,” Scientific Reports, vol. 7, no. 1, p. 16050, 2017.
View at: Publisher Site | Google Scholar
S. Z. Lepej, L. Mišić-Majerus, T. Jeren et al., “Chemokines CXCL10 and CXCL11 in the cerebrospinal fluid of patients with tick-borne encephalitis,” Acta Neurologica Scandinavica, vol. 115, no. 2, pp. 109–114, 2007.
View at: Publisher Site | Google Scholar
S. Kovats, S. Turner, A. Simmons, T. Powe, E. Chakravarty, and J. Alberola-Ila, “West Nile virus-infected human dendritic cells fail to fully activate invariant natural killer T cells,” Clinical and Experimental Immunology, vol. 186, no. 2, pp. 214–226, 2016.
View at: Publisher Site | Google Scholar
M. Kumar, S. Verma, and V. R. Nerurkar, “Pro-inflammatory cytokines derived from West Nile virus (WNV)-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death,” Journal of Neuroinflammation, vol. 7, no. 1, p. 73, 2010.
View at: Publisher Site | Google Scholar
H. J. Ramos, M. C. Lanteri, G. Blahnik et al., “IL-1β signaling promotes CNS-intrinsic immune control of West Nile virus infection,” PLoS Pathogens, vol. 8, no. 11, article e1003039, 2012.
View at: Publisher Site | Google Scholar
J. L. Chen, X. L. Niu, Y. L. Gao et al., “IL-18 knockout alleviates atopic dermatitis-like skin lesions induced by MC903 in a mouse model,” International Journal of Molecular Medicine, vol. 46, no. 2, pp. 880–888, 2020.
View at: Publisher Site | Google Scholar
U. C. Chaturvedi, R. Raghupathy, A. S. Pacsa et al., “Shift from a Th1-type response to Th2-type in dengue haemorrhagic fever,” Current Science, vol. 76, no. 1, pp. 63–69, 1999.
View at: Google Scholar
J. F. Navarro-González and C. Mora-Fernández, “The role of inflammatory cytokines in diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 19, no. 3, pp. 433–442, 2008.
View at: Publisher Site | Google Scholar
E. Dima, O. Koltsida, P. Katsaounou et al., “Implication of interleukin (IL)-18 in the pathogenesis of chronic obstructive pulmonary disease (COPD),” Cytokine, vol. 74, no. 2, pp. 313–317, 2015.
View at: Publisher Site | Google Scholar
M. Esmailbeig and A. Ghaderi, “Interleukin-18: a regulator of cancer and autoimmune diseases,” European Cytokine Network, vol. 28, no. 4, pp. 127–140, 2017.
View at: Publisher Site | Google Scholar
G. Palma, A. Barbieri, S. Bimonte et al., “Interleukin 18: friend or foe in cancer,” Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, vol. 1836, no. 2, pp. 296–303, 2013.
View at: Publisher Site | Google Scholar
I. H. Park, H. N. Yang, K. J. Lee et al., “Tumor-derived IL-18 induces PD-1 expression on immunosuppressive NK cells in triple-negative breast cancer,” Oncotarget, vol. 8, no. 20, pp. 32722–32730, 2017.
View at: Publisher Site | Google Scholar
R. Z. Harms, D. N. Yarde, Z. Guinn et al., “Increased expression of IL-18 in the serum and islets of type 1 diabetics,” Molecular Immunology, vol. 64, no. 2, pp. 306–312, 2015.
View at: Publisher Site | Google Scholar
E. L. Azeredo, P. C. Neves-Souza, A. R. Alvarenga et al., “Differential regulation of toll-like receptor-2, toll-like receptor-4, CD16 and human leucocyte antigen-DR on peripheral blood monocytes during mild and severe dengue fever,” Immunology, vol. 130, no. 2, pp. 202–216, 2010.
View at: Publisher Site | Google Scholar
E. L. Azeredo, S. M. Zagne, A. R. Alvarenga, R. M. Nogueira, C. F. Kubelka, and L. M. de Oliveira-Pinto, “Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease,” Memórias do Instituto Oswaldo Cruz, vol. 101, no. 4, pp. 437–449, 2006.
View at: Publisher Site | Google Scholar
M. B. Borges, R. S. Marchevsky, R. Carvalho Pereira et al., “Detection of post-vaccination enhanced dengue virus infection in macaques: an improved model for early assessment of dengue vaccines,” PLoS Pathogens, vol. 15, no. 4, article e1007721, 2019.
View at: Publisher Site | Google Scholar
V. V. Costa, C. T. Fagundes, D. F. Valadão et al., “A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-γ in host resistance to infection,” PLoS Neglected Tropical Diseases, vol. 6, no. 5, article e1663, 2012.
View at: Publisher Site | Google Scholar
C. T. Fagundes, V. V. Costa, D. Cisalpino et al., “IFN-γ production depends on IL-12 and IL-18 combined action and mediates host resistance to dengue virus infection in a nitric oxide-dependent manner,” PLoS Neglected Tropical Diseases, vol. 5, no. 12, article e1449, 2011.
View at: Publisher Site | Google Scholar
D. Paquin-Proulx, V. I. Avelino-Silva, B. A. N. Santos et al., “MAIT cells are activated in acute dengue virus infection and after in vitro Zika virus infection,” PLoS Neglected Tropical Diseases, vol. 12, no. 1, article e0006154, 2018.
View at: Publisher Site | Google Scholar
C. A. van de Weg, R. M. Huits, C. S. Pannuti et al., “Hyperferritinaemia in dengue virus infected patients is associated with immune activation and coagulation disturbances,” PLoS Neglected Tropical Diseases, vol. 8, no. 10, article e3214, 2014.
View at: Publisher Site | Google Scholar
G. Patra, B. Saha, and S. Mukhopadhyay, “The relationship between changes in IL-2 / IL-18 and liver enzyme with dengue severity,” Cytokine, vol. 148, p. 155713, 2021.
View at: Publisher Site | Google Scholar
A. S. Yeo, N. A. Azhar, W. Yeow et al., “Lack of clinical manifestations in asymptomatic dengue infection is attributed to broad down-regulation and selective up-regulation of host defence response genes,” PLoS One, vol. 9, no. 4, article e92240, 2014.
View at: Publisher Site | Google Scholar
V. E. Fiestas Solórzano, N. R. da Costa Faria, C. F. dos Santos et al., “Different profiles of cytokines, chemokines and coagulation mediators associated with severity in Brazilian patients infected with dengue virus,” Viruses, vol. 13, no. 9, p. 1789, 2021.
View at: Publisher Site | Google Scholar
Y. K. Yong, H. Y. Tan, S. H. Jen et al., “Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease,” Journal of Translational Medicine, vol. 15, no. 1, p. 121, 2017.
View at: Publisher Site | Google Scholar
A. Duran, N. Valero, J. Mosquera, E. Fuenmayor, and M. Alvarez-Mon, “Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures,” Life Sciences, vol. 191, pp. 180–185, 2017.
View at: Publisher Site | Google Scholar
A. Duran, N. Valero, J. Mosquera, L. Delgado, M. Alvarez-Mon, and M. Torres, “Role of the myeloid differentiation primary response (MYD88) and TIR-domain- containing adapter-inducing interferon-β (TRIF) pathways in dengue,” Life Sciences, vol. 162, pp. 33–40, 2016.
View at: Publisher Site | Google Scholar
C. Wen, Y. Yu, C. Gao, X. Qi, C. J. Cardona, and Z. Xing, “RIPK3-dependent necroptosis is induced and restricts viral replication in human astrocytes infected with Zika virus,” Frontiers in Cellular and Infection Microbiology, vol. 11, article 637710, 2021.
View at: Publisher Site | Google Scholar
J. Zmurko, R. E. Marques, D. Schols, E. Verbeken, S. J. Kaptein, and J. Neyts, “The viral polymerase inhibitor 7-deaza-2'-C-methyladenosine is a potent inhibitor of in vitro Zika virus replication and delays disease progression in a robust mouse infection model,” PLoS Neglected Tropical Diseases, vol. 10, no. 5, article e0004695, 2016.
View at: Publisher Site | Google Scholar
J. R. de Sousa, R. Azevedo, A. J. Martins Filho et al., “In situ inflammasome activation results in severe damage to the central nervous system in fatal Zika virus microcephaly cases,” Cytokine, vol. 111, pp. 255–264, 2018.
View at: Publisher Site | Google Scholar
D. K. Kaushik, M. Gupta, K. L. Kumawat, and A. Basu, “NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese encephalitis,” PLoS One, vol. 7, no. 2, article e32270, 2012.
View at: Publisher Site | Google Scholar
S. Kovats, S. Turner, A. Simmons, T. Powe, E. Chakravarty, and J. Alberola-Ila, “West Nile virus-infected human dendritic cells fail to fully activate invariant natural killer T cells,” Clinical and Experimental Immunology, vol. 186, no. 2, pp. 214–226, 2016.
View at: Publisher Site | Google Scholar
N. Marquardt, M. A. Ivarsson, K. Blom et al., “The human NK cell response to yellow fever virus 17D is primarily governed by NK cell differentiation independently of NK cell education,” Journal of Immunology, vol. 195, no. 7, pp. 3262–3272, 2015.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2021 Josephine Diony Nanda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

1485

Downloads

865

Citations