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Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.
Gideon, Hannah P; Hughes, Travis K; Tzouanas, Constantine N; Wadsworth, Marc H; Tu, Ang Andy; Gierahn, Todd M; Peters, Joshua M; Hopkins, Forrest F; Wei, Jun-Rong; Kummerlowe, Conner; Grant, Nicole L; Nargan, Kievershen; Phuah, Jia Yao; Borish, H Jacob; Maiello, Pauline; White, Alexander G; Winchell, Caylin G; Nyquist, Sarah K; Ganchua, Sharie Keanne C; Myers, Amy; Patel, Kush V; Ameel, Cassaundra L; Cochran, Catherine T; Ibrahim, Samira; Tomko, Jaime A; Frye, Lonnie James; Rosenberg, Jacob M; Shih, Angela; Chao, Michael; Klein, Edwin; Scanga, Charles A; Ordovas-Montanes, Jose; Berger, Bonnie; Mattila, Joshua T; Madansein, Rajhmun; Love, J Christopher; Lin, Philana Ling; Leslie, Alasdair; Behar, Samuel M; Bryson, Bryan; Flynn, JoAnne L; Fortune, Sarah M; Shalek, Alex K.
Affiliation
  • 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.
  • Hughes TK; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tzouanas CN; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wadsworth MH; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge,
  • Tu AA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Gierahn TM; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Peters JM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Hopkins FF; 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.
  • Wei JR; 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.
  • Kummerlowe C; Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Grant NL; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Nargan K; Africa Health Research Institute, Durban, South Africa.
  • Phuah JY; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Borish HJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Maiello P; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • White AG; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Winchell CG; 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; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pit
  • Nyquist SK; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Program in Computational and Systems Biology, Massachusetts Institute of T
  • Ganchua SKC; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Myers A; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Patel KV; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Ameel CL; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Cochran CT; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Ibrahim S; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tomko JA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Frye LJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, 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; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
  • Shih A; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, 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.
  • Klein E; Division of Laboratory Animal Research, University of Pittsburgh, Pittsburgh PA, 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.
  • Ordovas-Montanes J; Ragon Institute of MGH, MIT, and Harvard, 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.
  • Mattila JT; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • Madansein R; Department of Cardiothoracic Surgery, University of KwaZulu Natal, Durban, South Africa.
  • Love JC; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Lin PL; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
  • Leslie A; Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Department of Infection and Immunity, University College London, London, UK.
  • Behar SM; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
  • Bryson B; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, 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. Electronic address: joanne@pitt.edu.
  • Fortune SM; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: sfortune@hsph.harvard.edu.
  • Shalek AK; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge,
Immunity ; 55(5): 827-846.e10, 2022 05 10.
Article in En | MEDLINE | ID: mdl-35483355
Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal positron emission tomography and computed tomography imaging, single-cell RNA sequencing, and measures of bacterial clearance. Bacterial persistence occurred in granulomas enriched for mast, endothelial, fibroblast, and plasma cells, signaling amongst themselves via type 2 immunity and wound-healing pathways. Granulomas that drove bacterial control were characterized by cellular ecosystems enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-inflammatory signaling networks involving diverse cell populations. Granulomas that arose later in infection displayed functional characteristics of restrictive granulomas and were more capable of killing Mtb. Our results define the complex multicellular ecosystems underlying (lack of) granuloma resolution and highlight host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pulmonary Fibrosis / Tuberculosis / Mycobacterium tuberculosis Type of study: Prognostic_studies Limits: Animals Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2022 Document type: Article Affiliation country: Country of publication:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pulmonary Fibrosis / Tuberculosis / Mycobacterium tuberculosis Type of study: Prognostic_studies Limits: Animals Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2022 Document type: Article Affiliation country: Country of publication: