Author:
dos-Santos Júlio Souza,Firmino-Cruz Luan,Oliveira-Maciel Diogo,da Fonseca-Martins Alessandra Marcia,Ramos Tadeu Diniz,Nunes-Souza Letícia,Soares Rodrigo Pedro,Gomes Daniel Claudio Oliveira,Mengel José,Silva-Santos Bruno,de Matos Guedes Herbert Leonel
Abstract
Abstractγδ T cells are innate-like lymphocytes with pleiotropic roles in immune responses to pathogens, often ascribed to their IL-17A-producing or IFN-γ-producing γδ T cell subsets. Here we investigated the impact of this functional dichotomy on cutaneous leishmaniasis, a set of neglected diseases caused by parasites of theLeishmaniagenus. We demonstrate that in Sv129 mice susceptible toLeishmania amazonensis, Vγ4+γδ T cells are the main source of IL-17A. Furthermore, in type 1 interferon receptor-deficient (A129) mice presenting increased susceptibility to infection, there is a higher frequency of IL-17A-producing γδ T cells when compared to wild-type mice. Mechanistically, we demonstrate that lipophosphoglycan (LPG) ofL. amazonensisinduces IL-17A-producing γδ T cells. Importantly, C57Bl/6 mice deficient in γδ T cells or in IL-17 receptor (IL-17RA) show reduced lesion sizes, consistent with a pathogenic role of IL-17A-producing γδ T cells in cutaneous leishmaniasis. Conversely, the adoptive transfer of FACS-sorted γδ T cells led to an accumulation of IFN-γ-producing γδ T cells in various susceptible strains of mice which associated with control of lesion development. These data demonstrate a pathophysiological dichotomy in which IL-17A-producing γδ T cells promote pathogenesis, whereas IFN-γ-producing γδ T cells display therapeutic potential in cutaneous leishmaniasis.
Publisher
Cold Spring Harbor Laboratory
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