How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs.
العنوان: | How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs. |
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المؤلفون: | Zheng W, Borja M, Dorman L, Liu J, Zhou A, Seng A, Arjyal R, Sunshine S, Nalyvayko A, Pisco A, Rosenberg O, Neff N, Zha BS |
المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 22. Date of Electronic Publication: 2024 Apr 22. |
نوع المنشور: | Preprint |
اللغة: | English |
بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
مستخلص: | Mycobacterium tuberculosis (MTB) infects and replicates in lung mononuclear phagocytes (MNPs) with astounding ability to evade elimination. ESX-1, a type VII secretion system, acts as a virulence determinant that contributes to MTB's ability to survive within MNPs, but its effect on MNP recruitment and/or differentiation remains unknown. Here, using single-cell RNA sequencing, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow-derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden. Further, MTB induces an anti-inflammatory signature in MNPs and BMDM in an ESX-1 dependent manner. Similarly, spatial transcriptomics revealed an upregulation of anti-inflammatory signals in MTB lesions, where monocyte-derived macrophages concentrate near MTB-infected cells. Together, our findings suggest that MTB ESX-1 mediates the recruitment and differentiation of anti-inflammatory MNPs, which MTB can infect and manipulate for survival. |
معلومات مُعتمدة: | K08 HL163405 United States HL NHLBI NIH HHS |
تواريخ الأحداث: | Date Created: 20240507 Latest Revision: 20240712 |
رمز التحديث: | 20240712 |
مُعرف محوري في PubMed: | PMC11071417 |
DOI: | 10.1101/2024.04.20.590421 |
PMID: | 38712150 |
قاعدة البيانات: | MEDLINE |
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