CD8 +T cells require CCR5 expression to mediate immunopathology in cutaneous leishmaniasis

Abstract Cytolytic CD8 +T cells mediate immunopathology in cutaneous leishmaniasis by a mechanism dependent on degranulation and lysis of Leishmania-infected cells, culminating NLRP3 activation IL-1b release. Here, we sought to identify chemokine receptors involved cell migration the lesion that could be employed as treatment target ameliorate disease severity. A transcriptional study identified profile predicts failure Leishmania braziliensispatients identifies possible targets may migration. Using murine models leishmaniasis, found around 20% +T-cells express CCR5 lesions at peak disease. In previous studies, transferred Rag1 −/−mice mediated increased Therefore, test if expression was their lesions, wild-type or −/−CD8 L. braziliensisinfected −/−mice. While infected reconstituted with developed severe pathology, received smaller accompanied significant reduction number lesions. To whether blockade would control severity, used maraviroc (MVC), selective inhibitor approved FDA. MVC significantly reduced development without affecting parasite our models. Collectively, these results demonstrate cytolytic migrate leishmania CCR5-dependent manner, efficiently prevents +T-cell pathology. R01 AI106842 U01 AI08865006