Initiation of a primary cutaneous immune response. The skin is a primary immunological barrier to the external environment. The uppermost layer “corneal layer” is composed of dead keratinocytes that provide a physical barrier. However, the pathogens can access directly to the interior of the host through skin wounds and by outcompeting the normal flora (1). TLR-bearing cells (KCs and LCs) recognize pathogens and establish a highly coordinated immune response: antimicrobial production to neutralize the pathogen (2), inflammatory mediator secretion to alert the immune cells (3), activation of innate immune cells such as natural killer cells (NK) to induce cell lysis and/or phagocytosis such as macrophages to engulf pathogens (4), and maturation of dermal DCs that migrate into draining lymph nodes to prime T cell responses (adaptive immunity) (5).