Immunization with Leishmania major centrin knock-out (LmCen −/− ) parasites induces skin resident memory T cells that plays a role in protection against wild type infection (LmWT)

Abstract

Abstract Leishmaniasis is a vector-born disease transmitted through sand fly bite with no available vaccine. Vaccination through leishmanization with Leishmania major has been used successfully but is not safe. Recently, we have demonstrated immunization with live attenuated LmCen−/− parasite protects against Leishmaniasis via induction of host cellular immunity. Resident memory T cells (TRMs) are considered the first line of defense against infections invading the host through epithelial barrier. We evaluated the generation and function of skin TRMs post LmCen−/− immunization, compared to that generated by LmWT healed mice. We examined chemokine receptors controlling the generation and survival of skin TRMs, as well as effector and recruitment function of those cells post challenge with WT parasites. We observed that expression of CXCR6 and CXCR3 was significantly higher on T cells from spleens and lymph nodes of immunized mice, compared to those from healed mice. At 15 weeks post immunization, the skin of immunized mice had significantly larger population of TRMs compared to healed mice. In addition, epithelial cytokine production, such as IL-15, IL-33 and TNFa was significantly higher in the skin of immunized mice. Upon virulent challenge, immunofluorescent labeling of skin sections showed rapid recruitment of more T cells in the immunized mice compared to healed mice. IFNγ production by skin TRMs post challenge was significantly higher in immunized mice compared to healed mice. Taken together, these results show that immunization with live attenuated parasites is safer than Leishmanization. In addition, it generates large functional population of skin TRMs which play an important role in protection against the Leishmania infection.