Article ; Online: Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis.
2015 Volume 19, Issue 1, Page(s) 102–113
Abstract: Mutations in the autophagy gene EPG5 are linked to the multisystem human disease Vici syndrome ... in myeloid cells also led to elevated basal lung inflammation and influenza resistance. This suggests that Epg5 and ... lung inflammation and were resistant to lethal influenza virus infection. Lung transcriptomics ...
| Abstract | Mutations in the autophagy gene EPG5 are linked to the multisystem human disease Vici syndrome, which is characterized in part by pulmonary abnormalities, including recurrent infections. We found that Epg5-deficient mice exhibited elevated baseline innate immune cellular and cytokine-based lung inflammation and were resistant to lethal influenza virus infection. Lung transcriptomics, bone marrow transplantation experiments, and analysis of cellular cytokine expression indicated that Epg5 plays a role in lung physiology through its function in macrophages. Deletion of other autophagy genes including Atg14, Fip200, Atg5, and Atg7 in myeloid cells also led to elevated basal lung inflammation and influenza resistance. This suggests that Epg5 and other Atg genes function in macrophages to limit innate immune inflammation in the lung. Disruption of this normal homeostatic dampening of lung inflammation results in increased resistance to influenza, suggesting that normal homeostatic mechanisms that limit basal tissue inflammation support some infectious diseases. |
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| MeSH term(s) | Animals ; Autophagy-Related Protein 7 ; Autophagy-Related Proteins ; Homeostasis ; Humans ; Immunity, Innate ; Influenza A Virus, H1N1 Subtype/physiology ; Influenza, Human/genetics ; Influenza, Human/immunology ; Influenza, Human/virology ; Macrophages/immunology ; Mice ; Mice, Knockout ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/immunology ; Pneumonia/genetics ; Pneumonia/immunology ; Pneumonia/virology ; Proteins/genetics ; Proteins/immunology ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/immunology | |||||
| Chemical Substances | Atg14 protein, mouse ; Atg7 protein, mouse ; Autophagy-Related Proteins ; Epg5 protein, mouse ; Microtubule-Associated Proteins ; Proteins ; Vesicular Transport Proteins ; Autophagy-Related Protein 7 (EC 6.2.1.45) | |||||
| Language | English | |||||
| Publishing date | 2015-12-17 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2278004-X | |||||
| ISSN | 1934-6069 ; 1931-3128 | |||||
| ISSN (online) | 1934-6069 | |||||
| ISSN | 1931-3128 | |||||
| DOI | 10.1016/j.chom.2015.12.011 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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