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

Sang Min Jeon, Yeon Ju Lee, Sang-Hee Lee, Soo In Kim, Bomi Lee, Taylor Roh, Young Jae Kim, Hyeon Ji Kim, In Soo Kim, Jake Whang, So-young Kim, Byung Woo Jhun, Chaeuk Chung, Da Hyun Kang, Min-Kyung Yeo, Jin-Man Kim, Jichan Jang, Jung-Joon Min, Masaaki Komatsu, Jin Kyung Kim (), Woong-Yang Park () and Eun-Kyeong Jo ()
Additional contact information
Sang Min Jeon: Chungnam National University
Yeon Ju Lee: Sungkyunkwan University
Sang-Hee Lee: Korea Basic Science Institute
Soo In Kim: Chungnam National University
Bomi Lee: Chungnam National University
Taylor Roh: Chungnam National University
Young Jae Kim: Chungnam National University
Hyeon Ji Kim: Chungnam National University
In Soo Kim: Chungnam National University
Jake Whang: The Korean Institute of Tuberculosis (KIT)
So-young Kim: Chonnam National University Medical School
Byung Woo Jhun: Sungkyunkwan University
Chaeuk Chung: Chungnam National University Hospital
Da Hyun Kang: Chungnam National University Hospital
Min-Kyung Yeo: Chungnam National University Hospital
Jin-Man Kim: Chungnam National University Hospital
Jichan Jang: Gyeongsang National University
Jung-Joon Min: Chonnam National University Medical School
Masaaki Komatsu: Juntendo University
Jin Kyung Kim: Keimyung University
Woong-Yang Park: Sungkyunkwan University
Eun-Kyeong Jo: Chungnam National University

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61791-1

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