Immunological role of keratinocytes in leishmaniasis

Following inoculation of Leishmania, a protozoan parasite, into the skin of a mammal, the epidermal keratinocytes recognize the parasite and influence the local immune response that can give rise to different outcomes of leishmaniasis. The early keratinocyte-derived cytokines and keratinocytes-T cells interactions shape the anti-leishmanial immune responses that contribute to the resistance or susceptibility to leishmaniasis. The keratinocyte-derived cytokines can directly potentiate the leishmanicidal activity of monocytes and macrophages. As keratinocytes express MHC-II and enhance the expression of costimulatory molecules, these cells act as antigen-presenting cells (APCs) in cutaneous leishmaniasis (CL). Depending on the epidermal microenvironment, the keratinocytes induce various types of effector CD4⁺ T cells. Keratinocyte apoptosis and necrosis have been also implicated in ulceration in CL. Further, keratinocytes contribute to the healing of Leishmania-related cutaneous wounds. However, keratinocyte-derived IL-10 may play a key role in the development of post-kala-azar dermal leishmaniasis (PKDL). In this review, a comprehensive discussion regarding the multiple roles played by keratinocytes during leishmaniasis was provided, while highlighting novel insights concerning the immunological and pathological roles of these cells.