Author | dos-Santos, Júlio Souza | |
Author | Firmino-Cruz, Luan | |
Author | Oliveira-Maciel, Diogo | |
Author | Fonseca-Martins, Alessandra Marcia da | |
Author | Ramos, Tadeu Diniz | |
Author | Nunes-Souza, Letícia | |
Author | Soares, Rodrigo Pedro Pinto | |
Author | Gomes, Daniel Claudio Oliveira | |
Author | Mengel, José | |
Author | Silva-Santos, Bruno | |
Author | Guedes, Herbert Leonel de Matos | |
Access date | 2024-02-22T16:45:21Z | |
Available date | 2024-02-22T16:45:21Z | |
Document date | 2024 | |
Citation | SANTOS, Júlio Souza dos et al. IL-17A/IFN-γ producing γ δ T cell functional dichotomy impacts cutaneous leishmaniasis in mice. bioRxiv, 2024. https://doi.org/10.1101/2024.01.22.576494. | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/62741 | |
Language | eng | en_US |
Rights | restricted access | en_US |
Title | IL-17A/IFN-γ producing γ δ T cell functional dichotomy impacts cutaneous leishmaniasis in mice | en_US |
Type | Preprint | en_US |
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 | en_US |
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. | en_US |
Affilliation | Mucosal B cell Laboratory. Department of Pathology. New York University Langone Medical Center. New York, NY, USA. | en_US |
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. | en_US |
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. | en_US |
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. | en_US |
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. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas/Núcleo de Biotecnologia. Vitoria, ES, Brasil | en_US |
Affilliation | Clinical Immunology Laboratory. Oswaldo Cruz Institute. Oswaldo Cruz Foundation. Rio de Janeiro, RJ, Brazil. | en_US |
Affilliation | Institute of Molecular Medicine João Lobo Antunes. Faculty of Medicine of the University of Lisbon. Lisbon, Portugal. | en_US |
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. | en_US |
Embargo date | 2060-12-31 | |