MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathway

Mycobacterium abscessus subsp. abscessus (M.abs) is a nontuberculous mycobacterium that can infect human lung macrophages, which poses a public health concern. Understanding its mechanism is crucial for developing strategies to combat M.abs infections. M.abs survives within host cells by inhibiting...

Full description

Saved in:
Bibliographic Details
Main Authors: Dong Ho Kim, Kyungho Woo, Ho-Sung Park, Hye-Soo Park, Hwa-Jung Kim, Chul Hee Choi
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Virulence
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21505594.2025.2529493
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849321023710691328
author Dong Ho Kim
Kyungho Woo
Ho-Sung Park
Hye-Soo Park
Hwa-Jung Kim
Chul Hee Choi
author_facet Dong Ho Kim
Kyungho Woo
Ho-Sung Park
Hye-Soo Park
Hwa-Jung Kim
Chul Hee Choi
author_sort Dong Ho Kim
collection DOAJ
description Mycobacterium abscessus subsp. abscessus (M.abs) is a nontuberculous mycobacterium that can infect human lung macrophages, which poses a public health concern. Understanding its mechanism is crucial for developing strategies to combat M.abs infections. M.abs survives within host cells by inhibiting autophagy, a defense mechanism used against intracellular pathogens; therefore, we investigated the mechanism underlying autophagy inhibition and human lung macrophage infection by M.abs. This study focuses on the M.abs UC22 strain, which exhibits stronger inhibition of autophagic flux compared to the M.abs ATCC 19,977 strain. Central to this study is MAB_0676c, a protein secreted by M.abs UC22, and its effects on autophagic flux and the innate immune response, particularly its role in enhancing IL-10 production, a known autophagy regulator. Experiments showed that MAB_0676c expression stabilizes autophagy-related proteins while reducing LC3-LAMP2 co-localization in macrophages, thereby inhibiting autophagy and promoting bacterial growth. Furthermore, blocking IL-10 reduced both autophagy-related protein levels and the intracellular growth of MAB_0676c-expressing bacteria. Therefore, M.abs UC22 mediates intracellular survival by inhibiting autophagy through IL-10 production. Our study reveals bacterial immune-evasion tactics and identifies a potential therapeutic target for treating infectious diseases caused by nontuberculous mycobacteria.
format Article
id doaj-art-a6772f0d7cf44fd78051007123b3202b
institution Kabale University
issn 2150-5594
2150-5608
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
record_format Article
series Virulence
spelling doaj-art-a6772f0d7cf44fd78051007123b3202b2025-08-20T03:49:54ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2025.2529493MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathwayDong Ho Kim0Kyungho Woo1Ho-Sung Park2Hye-Soo Park3Hwa-Jung Kim4Chul Hee Choi5Department of Microbiology, School of Medicine, Chungnam National University, Daejeon, South KoreaDepartment of Microbiology, School of Medicine, Chungnam National University, Daejeon, South KoreaDepartment of Microbiology, School of Medicine, Chungnam National University, Daejeon, South KoreaDepartment of Microbiology, School of Medicine, Chungnam National University, Daejeon, South KoreaDepartment of Microbiology, School of Medicine, Chungnam National University, Daejeon, South KoreaDepartment of Microbiology, School of Medicine, Chungnam National University, Daejeon, South KoreaMycobacterium abscessus subsp. abscessus (M.abs) is a nontuberculous mycobacterium that can infect human lung macrophages, which poses a public health concern. Understanding its mechanism is crucial for developing strategies to combat M.abs infections. M.abs survives within host cells by inhibiting autophagy, a defense mechanism used against intracellular pathogens; therefore, we investigated the mechanism underlying autophagy inhibition and human lung macrophage infection by M.abs. This study focuses on the M.abs UC22 strain, which exhibits stronger inhibition of autophagic flux compared to the M.abs ATCC 19,977 strain. Central to this study is MAB_0676c, a protein secreted by M.abs UC22, and its effects on autophagic flux and the innate immune response, particularly its role in enhancing IL-10 production, a known autophagy regulator. Experiments showed that MAB_0676c expression stabilizes autophagy-related proteins while reducing LC3-LAMP2 co-localization in macrophages, thereby inhibiting autophagy and promoting bacterial growth. Furthermore, blocking IL-10 reduced both autophagy-related protein levels and the intracellular growth of MAB_0676c-expressing bacteria. Therefore, M.abs UC22 mediates intracellular survival by inhibiting autophagy through IL-10 production. Our study reveals bacterial immune-evasion tactics and identifies a potential therapeutic target for treating infectious diseases caused by nontuberculous mycobacteria.https://www.tandfonline.com/doi/10.1080/21505594.2025.2529493AutophagyIL-10macrophageMycobacterium abscessus subsp. abscessusRUBCN
spellingShingle Dong Ho Kim
Kyungho Woo
Ho-Sung Park
Hye-Soo Park
Hwa-Jung Kim
Chul Hee Choi
MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathway
Virulence
Autophagy
IL-10
macrophage
Mycobacterium abscessus subsp. abscessus
RUBCN
title MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathway
title_full MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathway
title_fullStr MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathway
title_full_unstemmed MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathway
title_short MAB_0676c-induced enhanced IL-10 production inhibits the autophagic flux via the MTOR/RUBCN pathway
title_sort mab 0676c induced enhanced il 10 production inhibits the autophagic flux via the mtor rubcn pathway
topic Autophagy
IL-10
macrophage
Mycobacterium abscessus subsp. abscessus
RUBCN
url https://www.tandfonline.com/doi/10.1080/21505594.2025.2529493
work_keys_str_mv AT donghokim mab0676cinducedenhancedil10productioninhibitstheautophagicfluxviathemtorrubcnpathway
AT kyunghowoo mab0676cinducedenhancedil10productioninhibitstheautophagicfluxviathemtorrubcnpathway
AT hosungpark mab0676cinducedenhancedil10productioninhibitstheautophagicfluxviathemtorrubcnpathway
AT hyesoopark mab0676cinducedenhancedil10productioninhibitstheautophagicfluxviathemtorrubcnpathway
AT hwajungkim mab0676cinducedenhancedil10productioninhibitstheautophagicfluxviathemtorrubcnpathway
AT chulheechoi mab0676cinducedenhancedil10productioninhibitstheautophagicfluxviathemtorrubcnpathway