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

ABSTRACT: Mycobacterium tuberculosis (Mtb) infects cells in multiple lung myeloid cell subsets and causes chronic infection despite innate and adaptive immune responses. However, the mechanisms allowing Mtb to evade elimination are not fully understood. Here, using new methods, we determined that after T cell responses have developed, CD11c^lo monocyte-derived lung cells termed MNC1 (mononuclear cell subset 1), harbor more live Mtb compared to alveolar macrophages (AM), neutrophils, and less permissive CD11c^hi MNC2. Bulk RNA sequencing of sorted cells revealed that the lysosome biogenesis pathway is underexpressed in MNC1. Functional assays confirmed that Mtb-permissive MNC1 have less lysosome content, acidification, and proteolytic activity than AM, and less nuclear TFEB

SUBMITTER: Zheng W 

PROVIDER: S-EPMC9882350 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature