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CD8+ lymphocytes are critical for early control of tuberculosis in macaques.
Winchell, Caylin G; Nyquist, Sarah K; Chao, Michael C; Maiello, Pauline; Myers, Amy J; Hopkins, Forrest; Chase, Michael; Gideon, Hannah P; Patel, Kush V; Bromley, Joshua D; Simonson, Andrew W; Floyd-O'Sullivan, Roisin; Wadsworth, Marc; Rosenberg, Jacob M; Uddin, Rockib; Hughes, Travis; Kelly, Ryan J; Griffo, Josephine; Tomko, Jaime; Klein, Edwin; Berger, Bonnie; Scanga, Charles A; Mattila, Joshua; Fortune, Sarah M; Shalek, Alex K; Lin, Philana Ling; Flynn, JoAnne L.
Afiliação
  • Winchell CG; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Nyquist SK; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Chao MC; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA.
  • Maiello P; Program in Computational and Systems Biology, Massachusetts Institute of Technology , Cambridge, MA, USA.
  • Myers AJ; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.
  • Hopkins F; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Chase M; Computer Science and Artificial Intelligence Laboratory and Department of Mathematics, MIT, Cambridge, MA, USA.
  • Gideon HP; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Patel KV; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Bromley JD; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA.
  • Simonson AW; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Floyd-O'Sullivan R; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA.
  • Wadsworth M; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Rosenberg JM; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Uddin R; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Hughes T; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA.
  • Kelly RJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Griffo J; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA.
  • Tomko J; Program in Computational and Systems Biology, Massachusetts Institute of Technology , Cambridge, MA, USA.
  • Klein E; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.
  • Berger B; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Scanga CA; Computer Science and Artificial Intelligence Laboratory and Department of Mathematics, MIT, Cambridge, MA, USA.
  • Mattila J; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Fortune SM; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA.
  • Shalek AK; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.
  • Lin PL; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Flynn JL; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.
J Exp Med ; 220(12)2023 12 04.
Article em En | MEDLINE | ID: mdl-37843832
ABSTRACT
The functional role of CD8+ lymphocytes in tuberculosis remains poorly understood. We depleted innate and/or adaptive CD8+ lymphocytes in macaques and showed that loss of all CD8α+ cells (using anti-CD8α antibody) significantly impaired early control of Mycobacterium tuberculosis (Mtb) infection, leading to increased granulomas, lung inflammation, and bacterial burden. Analysis of barcoded Mtb from infected macaques demonstrated that depletion of all CD8+ lymphocytes allowed increased establishment of Mtb in lungs and dissemination within lungs and to lymph nodes, while depletion of only adaptive CD8+ T cells (with anti-CD8ß antibody) worsened bacterial control in lymph nodes. Flow cytometry and single-cell RNA sequencing revealed polyfunctional cytotoxic CD8+ lymphocytes in control granulomas, while CD8-depleted animals were unexpectedly enriched in CD4 and γδ T cells adopting incomplete cytotoxic signatures. Ligand-receptor analyses identified IL-15 signaling in granulomas as a driver of cytotoxic T cells. These data support that CD8+ lymphocytes are required for early protection against Mtb and suggest polyfunctional cytotoxic responses as a vaccine target.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Mycobacterium tuberculosis Limite: Animals Idioma: En Revista: J Exp Med Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Mycobacterium tuberculosis Limite: Animals Idioma: En Revista: J Exp Med Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos