دورية أكاديمية
أعرض في EDS

Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.

التفاصيل البيبلوغرافية
العنوان: Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.
المؤلفون: Zheng W; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Chang IC; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Limberis J; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Budzik JM; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Zha BS; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America.; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Howard Z; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Chen L; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America., Ernst JD; Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America.
المصدر: PLoS pathogens [PLoS Pathog] 2024 May 03; Vol. 20 (5), pp. e1012205. Date of Electronic Publication: 2024 May 03 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Lysosomes*/metabolism , Lysosomes*/microbiology , Mycobacterium tuberculosis* , Monocytes*/metabolism , Monocytes*/microbiology , Macrophages, Alveolar*/microbiology , Macrophages, Alveolar*/metabolism, Animals ; Mice ; Lung/microbiology ; Lung/metabolism ; Mice, Inbred C57BL ; Chronic Disease ; Tuberculosis, Pulmonary/microbiology ; Tuberculosis, Pulmonary/metabolism ; Tuberculosis, Pulmonary/immunology ; Tuberculosis, Pulmonary/pathology ; Humans ; Tuberculosis/microbiology ; Tuberculosis/immunology ; Tuberculosis/metabolism ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
مستخلص: Mycobacterium tuberculosis (Mtb) infects lung myeloid cells, but the specific Mtb-permissive cells and host mechanisms supporting Mtb persistence during chronic infection are incompletely characterized. We report that after the development of T cell responses, CD11clo monocyte-derived cells harbor more live Mtb than alveolar macrophages (AM), neutrophils, and CD11chi monocyte-derived cells. Transcriptomic and functional studies revealed that the lysosome pathway is underexpressed in this highly permissive subset, characterized by less lysosome content, acidification, and proteolytic activity than AM, along with less nuclear TFEB, a regulator of lysosome biogenesis. Mtb infection does not drive lysosome deficiency in CD11clo monocyte-derived cells but promotes recruitment of monocytes that develop into permissive lung cells, mediated by the Mtb ESX-1 secretion system. The c-Abl tyrosine kinase inhibitor nilotinib activates TFEB and enhances lysosome functions of macrophages in vitro and in vivo, improving control of Mtb infection. Our results suggest that Mtb exploits lysosome-poor lung cells for persistence and targeting lysosome biogenesis is a potential host-directed therapy for tuberculosis.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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معلومات مُعتمدة: K08 HL163405 United States HL NHLBI NIH HHS; R01 AI051242 United States AI NIAID NIH HHS; U01 AI166309 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20240503 Date Completed: 20240515 Latest Revision: 20240712
رمز التحديث: 20240712
مُعرف محوري في PubMed: PMC11095722
DOI: 10.1371/journal.ppat.1012205
PMID: 38701094
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1012205