연구성과 홍보

Nat Commun. 2025 Jul 29;16(1):6966.

Title : ATG7 in innate immune cells is required for host defense against nontuberculous mycobacterial pulmonary infections

Authors : Sang Min Jeon#1,2,3, Yeon Ju Lee#4, Sang-Hee Lee#5,6, Soo In Kim#1,2,3, Bomi Lee1,2,3, Taylor Roh1,2,3, Young Jae Kim1,2,3, Hyeon Ji Kim1,2,3, In Soo Kim2,3,7,8, Jake Whang9, So-Young Kim10, Byung Woo Jhun11, Chaeuk Chung8,12, Da Hyun Kang8,12, Min-Kyung Yeo8,13, Jin-Man Kim8,13, Jichan Jang14, Jung-Joon Min10,15, Masaaki Komatsu16, Jin Kyung Kim17*, Woong-Yang Park18,19,20*, Eun-Kyeong Jo21,22,23,24*

Affiliations :

1Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

2Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

3Brain Korea 21 FOUR Project for Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

4Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.

5Center for Research Equipment, Korea Basic Science Institute, Cheongju, Republic of Korea.

6Department of Chemistry, Hanyang University, Seoul, Republic of Korea.

7Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

8Biomedical Research Institute, Chungnam National University Hospital, Daejeon, Republic of Korea.

9Korea Mycobacterium Resource Center (KMRC) & Basic Research Section, The Korean Institute of Tuberculosis (KIT), Cheongju, Republic of Korea.

10Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.

11Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.

12Division of Pulmonary and Critical Care, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

13Department of Pathology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

14Division of Life Science, Department of Bio & Medical Big Data (BK21 Four Program), Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.

15Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.

16Department of Physiology, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

17Department of Microbiology, School of Medicine, Keimyung University, Daegu, Republic of Korea.

18Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.

19Samsung Genome Institute, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.

20Geninus Inc., Seoul, Republic of Korea.

21Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

22Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. .

23Brain Korea 21 FOUR Project for Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.

24Biomedical Research Institute, Chungnam National University Hospital, Daejeon, Republic of Korea.

DOI: 10.1038/s41467-025-61791-1.

Abstract :

Infections caused by nontuberculous mycobacteria, such as Mycobacterium avium and Mycobacteroides abscessus, are becoming increasingly prevalent, and rising antibiotic resistance poses a significant clinical challenge. However, the mechanisms by which the host defense system controls these infections remain poorly understood. Here we show that the autophagy-related protein ATG7 in innate immune cells plays an essential role in controlling nontuberculous mycobacterial infection and protecting lung tissue from pathological inflammation. Patients with nontuberculous mycobacterial pulmonary disease exhibit reduced ATG7 expression in blood mononuclear cells and decreased ATG7 levels in necrotic lesions at disease sites. Mice lacking Atg7 in innate immune cells display elevated bacterial loads, excessive inflammation, mitochondrial damage, and multiple forms of cell death in the lungs, including pyroptosis, necrosis, and apoptosis. Notably, neutrophil infiltration in the lungs of these mice plays a key role in driving exacerbated inflammation and gasdermin E-associated cell death, which precede bacterial overgrowth. In vitro, Atg7-deficient macrophages exhibit impaired antimicrobial responses and reduced phagolysosomal fusion, but only modest increases in inflammation and cell death. These findings underscore the critical role of ATG7 in innate immune cells in orchestrating an effective host defense against nontuberculous mycobacterial lung infection by mitigating neutrophil-driven pathological inflammation and associated cell death.