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2060-12-31
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IL-17A/IFN-γ PRODUCING γ δ T CELL FUNCTIONAL DICHOTOMY IMPACTS CUTANEOUS LEISHMANIASIS IN MICE
Author
Affilliation
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Mucosal B cell Laboratory. Department of Pathology. New York University Langone Medical Center. New York, NY, USA.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas/Núcleo de Biotecnologia. Vitoria, ES, Brasil
Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Institute of Molecular Medicine João Lobo Antunes. Faculty of Medicine of the University of Lisbon. Lisbon, Portugal.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Mucosal B cell Laboratory. Department of Pathology. New York University Langone Medical Center. New York, NY, USA.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas/Núcleo de Biotecnologia. Vitoria, ES, Brasil
Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Institute of Molecular Medicine João Lobo Antunes. Faculty of Medicine of the University of Lisbon. Lisbon, Portugal.
Immunobiotechnology Laboratory. Institute of Microbiology Paulo de Góes. Federal University of Rio de Janeiro. Rio de Janeiro, RJ, RJ, Brazil/Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil.
Abstract
γδ T cells are innate-like lymphocytes with pleiotropic roles in immune responses to pathogens, often ascribed to their IL-17A-producing or IFN--producing T cellsubsets. Here we investigated the impact of this functional dichotomy on cutaneous leishmaniasis, a set of neglected diseases caused by parasites of the Leishmania genus. We demonstrate that in Sv129 mice susceptible to Leishmania amazonensis, V4 + 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-17Aproducing γδ T cells when compared to wild-type mice. Mechanistically, we demonstrate that lipophosphoglycan (LPG) of L. amazonensis induces 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
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