Ali  Ouaissi

Immunology and Molecular Biology of Protozoan Infections

Leishmania infection consists in two sequential events, the host cell 
 colonization followed by the proliferation/dissemination of the parasite. In this review, we discuss
 the importance of two distinct sets of molecules, the secreted and/or surface and the nonsecreted
 antigens. The importance of the immune response against secreted and surface antigens is 
 noted in the establishment of the infection and we dissect the contribution of the nonsecreted 
 antigens in the immunopathology associated with leishmaniasis, showing the importance of these 
 panantigens during the course of the infection. As a further example of proteins belonging to these
 two different groups, we include several laboratorial observations on Leishmania
 Sir2 and LicTXNPx as excreted/secreted proteins and LmS3arp 
 and 
LimTXNPx as nonsecreted/panantigens. The role of these two groups of antigens 
in the immune response observed during the infection is discussed.

Nuno Santarém

Ricardo Silvestre

Joana Tavares

Marta Silva

Sofia Cabral

Joana Maciel

Anabela Cordeiro-da-Silva

Immune Response Regulation by Leishmania Secreted and Nonsecreted Antigens

Over the past 15 years, DNA vaccines have gone from a scientific curiosity to one 
    of the most dynamic research field and may offer new alternatives for the control of 
    parasitic diseases such as leishmaniasis and Chagas disease. We review here some 
    of the advances and challenges for the development of DNA vaccines against these 
    diseases. Many studies have validated the concept of using DNA vaccines for both protection 
    and therapy against these protozoan parasites in a variety of mouse models. The challenge
     now is to translate what has been achieved in these models into veterinary or human vaccines 
     of comparable efficacy. Also, genome-mining and new antigen discovery strategies may provide 
     new tools for a more rational search of novel vaccine candidates.

Eric Dumonteil

DNA Vaccines against Protozoan Parasites:  Advances and Challenges

In an attempt to investigate the effects of treatment of human leishmaniasis, 
the cytokines produced by peripheral blood mononuclear cells (PBMCs) of patients with 
cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) under treatment 
with amphotericin B were determined during the active disease from cocultures of cells 
and Leishmania (Viannia) braziliensis antigens. PBMC of these patients 
exhibited a nonsignificant marginal increased production of TNF-<mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>α</mml:mi></mml:math> upon antigen stimulation. However, under the same antigenic 
stimulus, patients with active MCL presented higher IFN-<mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>γ</mml:mi></mml:math> production compared to patients with CL. This increased IFN-<mml:math id="E4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>γ</mml:mi></mml:math> production was accompanied by a drastically augmented IL-12 synthesis 
from cells of MCL patients. The highlighted T cell responses could be relevant for sound 
control measures of protozoan infections with emphasis on the combined usage of 
immunoenhancing agents and antiprotozoal drugs.

Washington R. Cuna

Rianed Velasquez

Janeth Riva

Ingrid Guachalla

Celeste Rodríguez

Enhancement of a <svg style="vertical-align:-3.27605pt" height="15.675" version="1.1" viewBox="0 0 20.35 15.675" width="20.35" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,11.537)"><path id="x54" d="M592 498l-30 -3q-13 63 -31 89q-13 19 -33.5 25.5t-75.5 6.5h-70v-493q0 -60 16 -75.5t86 -19.5v-28h-286v28q68 4 83.5 19.5t15.5 75.5v493h-62q-60 0 -83 -7t-33 -24q-12 -17 -32 -90h-29q10 116 12 180h20q10 -16 21 -20.5t34 -4.5h395q19 0 28.5 5t21.5 20h21&#xA;q2 -89 11 -177z" /></g><g transform="matrix(.012,-0,0,-.012,10.55,15.613)"><path id="x48" d="M729 650v-28q-62 -5 -76 -19.5t-14 -75.5v-404q0 -62 13.5 -76t75.5 -19v-28h-268v28q65 5 79.5 19t14.5 76v199h-341v-199q0 -62 14 -76t76 -19v-28h-263v28q61 5 74.5 19t13.5 76v404q0 62 -14 76t-76 19v28h259v-28q-58 -5 -71 -19t-13 -76v-162h341v162&#xA;q0 61 -13.5 75.5t-72.5 19.5v28h261z" /></g></svg> 1 Immune Response in Amphotericin B-Treated Mucocutaneous Leishmaniasis

Cytoadherence of Plasmodium-falciparum-parasitized 
 red blood cells (PRBCs) to host receptors is the key phenomenon in 
 the pathological process of the malaria disease. Some of these interactions can 
 originate poor outcomes responsible for 1 to 3 million annual deaths mostly occurring 
 among children in sub-Saharan Africa. Pregnancy-associated malaria (PAM) represents 
 an important exception of the disease occurring at adulthood in malaria endemic 
 settings. Consequences of this are shared between the mother (maternal anemia) and 
 the baby (low birth weight and infant mortality). Demonstrating that parasites causing 
 PAM express specific variant surface antigens (<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mrow><mml:mtext>VSA</mml:mtext></mml:mrow><mml:mrow><mml:mtext>PAM</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math>), including the P. falciparum erythrocyte membrane 
protein 1 (<mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>Pf</mml:mi></mml:mrow></mml:math>EMP1) variant VAR2CSA, that are targets for protective 
 immunity has strengthened the possibility for the development of PAM-specific
 vaccine. In this paper, we review the molecular basis of malaria pathogenesis attributable 
 to the erythrocyte stages of the parasites, and findings supporting potential anti-PAM
 vaccine components evidenced in PAM.

Nicaise Tuikue Ndam

Philippe Deloron

Molecular Aspects of Plasmodium falciparum Infection during Pregnancy

Parasitic infections are prevalent in both tropical and subtropical 
        areas. Most of the affected and/or exposed populations are living in 
        developing countries where control measures are lacking or inadequately applied. 
        Although significant progress has been made in our understanding of 
        the immune response to parasites, no definitive step has yet been successfully 
        done in terms of operational vaccines against parasitic diseases. 
        Evidence accumulated during the past few years suggests that the 
        pathology observed during parasitic infections is in part due to deregulation 
        of normal components of the immune system, mainly cytokines, 
        antibodies, and immune effector cell populations. A large number 
        of studies that illustrate how parasites can modify the host immune 
        system for their own benefit have been reported in both metazoan and 
        protozoan parasites. The first line of defense against foreign organisms 
        is barrier tissue such as skin, humoral factors, for instance the complement system 
        and pentraxin, which upon activation of the complement cascade 
facilitate pathogen recognition by cells of innate immunity 
such as macrophages and DC. However, all the major groups of parasites studied have been shown to contain and/or to release factors, which interfere with both arms of the host immune system. Even some astonishing observations relate to the production by some parasites of orthologues of mammalian cytokines. Furthermore, chronic parasitic infections have led to the immunosuppressive environment that correlates with increased levels of myeloid and T suppressor cells that may limit the success of immunotherapeutic strategies based on vaccination. This minireview briefly analyzes some of the current data related to the regulatory cells and molecules derived from parasites that affect cellular function and contribute to the polarization of the immune response of the host. Special attention is given to some of the data from our laboratory illustrating the role of immunomodulatory factors released by protozoan parasites, in the induction and perpetuation of chronic disease.

Ali Ouaissi

Regulatory Cells and Immunosuppressive Cytokines: 
      Parasite-Derived Factors  Induce Immune Polarization

Cytokine-mediated immunity is crucial in the defense against pathogens.
Recently, IL-23 and IL-27 were identified, which along with IL-12 belong to
the IL-12 cytokine family. IL-27 is pivotal for the induction of helper T
cell (Th) 1 responses while IL-23 is important for the proliferation of
memory type Th1 cells. Recent studies revealed that IL-27 also has an
anti-inflammatory property. In some protozoan infection, various
proinflammatory cytokines were over produced causing lethal inflammatory
responses in IL-27 receptor-deficient mice. The anti-inflammatory effect of
IL-27 depends, at least partly, on inhibition of the development of Th17
cells, a newly identified Th population that is induced by IL-23 and is
characterized by the production of the inflammatogenic cytokine, IL-17.
IL-27 thus has a double identity as an initiator and as an attenuator of
immune responses and inflammation. With the discoveries of the new
IL-12-related cytokines and Th17 cells, Th development is facing a new
paradigm.

Hiroki Yoshida

Yoshiyuki Miyazaki

Sen Wang

Shinjiro Hamano

Regulation of Defense Responses against Protozoan Infection by Interleukin-27 and Related Cytokines

Activation of the immune system against protozoan infections relies
particularly on two specific signals provided by cognate interaction of T
cells with antigen presenting cells (APCs). The first signal is attributed
to binding of the T-cell receptor (TCR) to peptide/MHC complexes on the
surface of APCs, whereas the second signal is triggered through binding of
several costimulatory molecules on the surface of APCs with their
corresponding receptors on T cells. Among these costimulatory signallings,
CD40/CD40L interactions have been particularly investigated in protozoan
infection models with regard to their potential to amplify cell-mediated
immunity against intracellular parasites. This article reviews current
studies of the potential role of CD40/CD40L interaction in the modulation of
immune responses against some protozoan parasites and highlights recent
developments regarding manipulation of this interaction for promoting
control of parasite infections.

Mustapha  Chamekh

CD40-CD40L Interaction in Immunity Against Protozoan Infections

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Immunology and Molecular Biology of Protozoan Infections

Immunology and Molecular Biology of Protozoan Infections

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