The lung is protected from spontaneous inflammation by autophagy in myeloid cells.
The lung is constantly exposed to the outer environment; thus, it must maintain a state of immune ignorance or tolerance not to overrespond to harmless environmental stimuli. How cells in the lung control immune responses under nonpathogenic condition is not fully understood. In this study, we found that autophagy plays a critical role in the lung-specific immune regulation that prevents spontaneous inflammation. Autophagy in pulmonary myeloid cells plays a role in maintaining low burdens of environmental microbes in the lung, as well as in lowering mitochondrial reactive oxygen species production and preventing overresponse to TLR4 ligands in alveolar macrophages. Based on these mechanisms, we also found that intranasal instillation of antibiotics or an inhibitor of reactive oxygen species was efficient in preventing spontaneous pulmonary inflammation. Thus, autophagy in myeloid cells, particularly alveolar macrophages, is critical for inhibiting spontaneous pulmonary inflammation, and pulmonary inflammation caused by dysfunctional autophagy is pharmacologically prevented.
Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
Masashi
M
Kanayama
Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
You-Wen
YW
He
Department of Immunology, Duke University Medical Center, Durham, NC 27710; and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 mari.shinohara@duke.edu.
Mari L
ML
Shinohara
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001343:Autophagy / Q000235:genetics* / Q000276:immunology; D000071193:Autophagy-Related Protein 7; D002478:Cells, Cultured; D004781:Environmental Exposure / Q000009:adverse effects; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008928:Mitochondria / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology*; D011014:Pneumonia / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology
D000900:Anti-Bacterial Agents; C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000071193:Autophagy-Related Protein 7