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Early cellular mechanisms of type I interferon-driven susceptibility to tuberculosis.
Kotov, Dmitri I; Lee, Ophelia V; Fattinger, Stefan A; Langner, Charlotte A; Guillen, Jaresley V; Peters, Joshua M; Moon, Andres; Burd, Eileen M; Witt, Kristen C; Stetson, Daniel B; Jaye, David L; Bryson, Bryan D; Vance, Russell E.
  • Kotov DI; Division of Immunology and Molecular Medicine, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: dkotov@berkeley.edu.
  • Lee OV; Division of Immunology and Molecular Medicine, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Fattinger SA; Division of Immunology and Molecular Medicine, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Langner CA; Division of Immunology and Molecular Medicine, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Guillen JV; Division of Immunology and Molecular Medicine, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Peters JM; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Moon A; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
  • Burd EM; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
  • Witt KC; Division of Immunology and Molecular Medicine, University of California, Berkeley, Berkeley, CA 94720, USA.
  • Stetson DB; Department of Immunology, University of Washington, Seattle, WA 98195, USA.
  • Jaye DL; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
  • Bryson BD; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Vance RE; Division of Immunology and Molecular Medicine, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: rvance@berkeley.edu.
Cell ; 186(25): 5536-5553.e22, 2023 12 07.
Article en En | MEDLINE | ID: mdl-38029747
ABSTRACT
Mycobacterium tuberculosis (Mtb) causes 1.6 million deaths annually. Active tuberculosis correlates with a neutrophil-driven type I interferon (IFN) signature, but the cellular mechanisms underlying tuberculosis pathogenesis remain poorly understood. We found that interstitial macrophages (IMs) and plasmacytoid dendritic cells (pDCs) are dominant producers of type I IFN during Mtb infection in mice and non-human primates, and pDCs localize near human Mtb granulomas. Depletion of pDCs reduces Mtb burdens, implicating pDCs in tuberculosis pathogenesis. During IFN-driven disease, we observe abundant DNA-containing neutrophil extracellular traps (NETs) described to activate pDCs. Cell-type-specific disruption of the type I IFN receptor suggests that IFNs act on IMs to inhibit Mtb control. Single-cell RNA sequencing (scRNA-seq) indicates that type I IFN-responsive cells are defective in their response to IFNγ, a cytokine critical for Mtb control. We propose that pDC-derived type I IFNs act on IMs to permit bacterial replication, driving further neutrophil recruitment and active tuberculosis disease.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Tuberculosis / Interferón Tipo I Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
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PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Tuberculosis / Interferón Tipo I Límite: Animals / Humans Idioma: En Año: 2023 Tipo del documento: Article