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Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung.
Pisu, Davide; Huang, Lu; Narang, Vipin; Theriault, Monique; Lê-Bury, Gabrielle; Lee, Bernett; Lakudzala, Agnes E; Mzinza, David T; Mhango, David V; Mitini-Nkhoma, Steven C; Jambo, Kondwani C; Singhal, Amit; Mwandumba, Henry C; Russell, David G.
Afiliación
  • Pisu D; Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY.
  • Huang L; Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY.
  • Narang V; Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR.
  • Theriault M; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
  • Lê-Bury G; Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY.
  • Lee B; Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY.
  • Lakudzala AE; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
  • Mzinza DT; Malawi Liverpool Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi.
  • Mhango DV; Malawi Liverpool Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi.
  • Mitini-Nkhoma SC; Malawi Liverpool Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi.
  • Jambo KC; Malawi Liverpool Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi.
  • Singhal A; Malawi Liverpool Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi.
  • Mwandumba HC; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
  • Russell DG; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
J Exp Med ; 218(9)2021 09 06.
Article en En | MEDLINE | ID: mdl-34292313
In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and bacterial phenotype for each infected cell. This approach facilitates the dissection of the functional heterogeneity of M. tuberculosis-infected alveolar (AMs) and interstitial macrophages (IMs) in vivo. We identify clusters of pro-inflammatory AMs associated with stressed bacteria, in addition to three different populations of IMs with heterogeneous bacterial phenotypes. Finally, we show that the main macrophage populations in the lung are epigenetically constrained in their response to infection, while inter-species comparison reveals that most AMs subsets are conserved between mice and humans. This conceptual approach is readily transferable to other infectious disease agents with the potential for an increased understanding of the roles that different host cell populations play during the course of an infection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis Pulmonar / Macrófagos Alveolares / Mycobacterium tuberculosis Límite: Animals / Humans Idioma: En Revista: J Exp Med Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis Pulmonar / Macrófagos Alveolares / Mycobacterium tuberculosis Límite: Animals / Humans Idioma: En Revista: J Exp Med Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos