التفاصيل البيبلوغرافية
| العنوان: |
Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection. |
| المؤلفون: |
Zheng W; University of California, San Francisco., Chang IC; University of California, San Francisco., Limberis J; University of California., Budzik J; University of California, San Francisco., Zha BS; University of California, San Francisco., Howard Z; University of California, San Francisco., Chen L; University of California, San Francisco., Ernst J; University of California San Francisco. |
| المصدر: |
Research square [Res Sq] 2023 Jun 15. Date of Electronic Publication: 2023 Jun 15. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE |
| مستخلص: |
Mycobacterium tuberculosis (Mtb) persists in lung myeloid cells during chronic infection. However, the mechanisms allowing Mtb to evade elimination are not fully understood. Here, we determined that in chronic phase, CD11c lo monocyte-derived lung cells termed MNC1 (mononuclear cell subset 1), harbor more live Mtb than alveolar macrophages (AM), neutrophils, and less permissive CD11c hi MNC2. Transcriptomic and functional studies of sorted cells revealed that the lysosome biogenesis pathway is underexpressed in MNC1, which have less lysosome content, acidification, and proteolytic activity than AM, and less nuclear TFEB, a master regulator of lysosome biogenesis. Mtb infection does not drive lysosome deficiency in MNC1. Instead, Mtb recruits MNC1 and MNC2 to the lungs for its spread from AM to these cells via its ESX-1 secretion system. The c-Abl tyrosine kinase inhibitor nilotinib activates TFEB and enhances lysosome function of primary macrophages and MNC1 and MNC2 in vivo, improving control of Mtb infection. Our results indicate that Mtb exploits lysosome-poor monocyte-derived cells for in vivo persistence, suggesting a potential target for host-directed tuberculosis therapy.
Competing Interests: Competing interests The authors declare that they have no competing interests. |
| التعليقات: |
Update in: PLoS Pathog. 2024 May 3;20(5):e1012205. (PMID: 38701094) |
| معلومات مُعتمدة: |
R01 AI051242 United States AI NIAID NIH HHS; T32 HL125232 United States HL NHLBI NIH HHS |
| تواريخ الأحداث: |
Date Created: 20230703 Latest Revision: 20240515 |
| رمز التحديث: |
20240515 |
| مُعرف محوري في PubMed: |
PMC10312915 |
| DOI: |
10.21203/rs.3.rs-3049913/v1 |
| PMID: |
37398178 |
| قاعدة البيانات: |
MEDLINE |
