Hypoxia and IL-15 Cooperate to Induce Perforin Expression by CD8 T Cells and Promote Damage to the Skin in Murine Cutaneous Leishmaniasis

Abstract

Cutaneous leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania , and although parasites influence disease severity, cytotoxic CD8 T-cell responses mediate damage to the infected skin. We found that the cytotoxic protein perforin was expressed in CD8 T cells only upon recruitment to Leishmania -infected skin, suggesting that lesional inflammatory cues induced perforin. In this study, using a mouse model of Leishmania major infection, we demonstrated that the expression of perforin was driven by a combination of hypoxia and IL-15, both of which are microenvironmental signals present within Leishmania -infected skin. We also demonstrated that the major sources of Il1..