IL-17A/IFN-γ producing γδ T cell functional dichotomy impacts cutaneous leishmaniasis in mice

Abstract

γδ T cells play diverse roles in immune responses, producing either IL-17A or IFN-γ. Here we investigated the impact of this functional dichotomy on cutaneous leishmaniasis. We demonstrate that in Sv129 mice susceptible to Leishmania amazonensis, Vγ4+ γδ T cells are the main source of IL-17A. In type 1 interferon receptor-deficient (A129) mice with heightened susceptibility, there is an increased frequency of IL-17A-producing γδ T cells. L. amazonensis’s lipophosphoglycan induces these IL-17A-producing γδ T cells. Notably, C57Bl/6 mice deficient in γδ T cells or IL-17 receptor exhibit smaller lesions, indicating a pathogenic role of IL-17A-producing γδ T cells in cutaneous leishmaniasis. Conversely, adoptive transfer of FACS-sorted γδ T cells lead to an accumulation of IFN-γ-producing γδ T cells, associated with control of lesion development. On the other hand, adoptive transfer of FACS-sorted IFN- γ- deficient-γδ T cells abolished the control of lesion development. These data demonstrate a pathophysiological dichotomy where IL-17A-producing γδ T cells promote pathogenesis, while IFN-γ-producing γδ T cells offer therapeutic potential in cutaneous leishmaniasis.