CD4 + T cells are homeostatic regulators during Mtb reinfection.

Autor:	Bromley JD; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Graduate Program in Microbiology, Massachusetts Institute of Technology, Cambridge, MA, USA., Ganchua SKC; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA.; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA., Nyquist SK; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA., Maiello P; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA., Chao M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Borish HJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA.; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA., Rodgers M; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA.; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA., Tomko J; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA.; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA., Kracinovsky K; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA.; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA., Mugahid D; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Nguyen S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Wang D; Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA., Rosenberg JM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Klein EC; Division of Laboratory Animal Research, University of Pittsburgh, Pittsburgh, PA, USA., Gideon HP; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA.; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA., Floyd-O'Sullivan R; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Berger B; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA., Scanga CA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA.; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA., Lin PL; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA.; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine., Fortune SM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Shalek AK; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.; Institute for Medical Engineering and Science (IMES), Massachusetts Institute of Technology, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Flynn JL; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh PA USA.; Center for Vaccine Research, University of Pittsburgh, Pittsburgh PA USA.; Lead contact.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 21. Date of Electronic Publication: 2023 Dec 21.
DOI:	10.1101/2023.12.20.572669
Abstrakt:	Immunological priming - either in the context of prior infection or vaccination - elicits protective responses against subsequent Mycobacterium tuberculosis ( Mtb ) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Here, using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrate that prior Mtb infection elicits a long-lasting protective response against subsequent Mtb exposure and that the depletion of CD4 + T cells prior to Mtb rechallenge significantly abrogates this protection. Leveraging microbiologic, PET-CT, flow cytometric, and single-cell RNA-seq data from primary infection, reinfection, and reinfection-CD4 + T cell depleted granulomas, we identify differential cellular and microbial features of control. The data collectively demonstrate that the presence of CD4 + T cells in the setting of reinfection results in a reduced inflammatory lung milieu characterized by reprogrammed CD8 + T cell activity, reduced neutrophilia, and blunted type-1 immune signaling among myeloid cells, mitigating Mtb disease severity. These results open avenues for developing vaccines and therapeutics that not only target CD4 + and CD8 + T cells, but also modulate innate immune cells to limit Mtb disease. Competing Interests: DECLARATIONS OF INTERESTS A.K.S. reports compensation for consulting and/or scientific advisory board membership from Honeycomb Biotechnologies, Cellarity, Ochre Bio, Relation Therapeutics, FL86, IntrECate Biotherapeutics, Bio-Rad Laboratories, Senda Biosciences and Dahlia Biosciences unrelated to this work. S.M.F. reports compensation for board of directors membership from Oxford Nanopore unrelated to this work.
Databáze:	MEDLINE
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