Characterization of Leishmania-Specific T cells in human skin and blood during cutaneous and mucocutaneous leishmaniasis

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Parasites belonging to the genus Leishmania are among the most diverse of human pathogens, both in terms of geographical distribution and in the variety of clinical syndromes caused by them. Currently, 12 million people are infected worldwide in 88 tropical/subtropical countries, 2 million new infections are reported annually, and 350 million people are under infection risk. In the past decade, the number of cases in endemic areas has increased sharply. In addition, leishmaniasis is spreading to several non-endemic areas of the world due to coinfections with HIV. Control measures currently available are case detection and treatment with drugs, which are expensive, not always available and cannot be self-administered. The problem is further aggravated by the surge of drug resistance parasites necessitating the development of an anti-Leishmania vaccine or other immunological therapies urgent. Research has demonstrated the importance of the immunity in controlling both cutaneous and mucocotaneous leishmaniasis, however the majority of this work has been performed on blood samples taken from patients and not from the site of infection at the skin. In this context, the current project aims to characterize the immune mechanisms involved in controlling Leishmania in both the blood and the skin. In this proposal, we aim to apply this established approach for the first time in studies with human localized cutaneous (LCL) and mucocutaneous leishmaniasis (MCL) in order to understand the immune mechanisms associated to cell development, function and regulation in the skin and blood. Through this work we will be able to identify in detail components of the cutaneous and systemic immunity that are involved during infection and determine which of these factor can drive lesion development or/and parasite control. The results will also provide important data that will increase the understanding of Leishmania immunity providing explanations about pathological differences observed in cutaneous and mucocotaneous leishmaniasis patients and contribute to the improved design of future vaccines and drug target.