Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2016 Jan 15

PMID 26764600

Citations 58

Authors

Qun Lu

Christine C Yokoyama

Jesse W Williams

Megan T Baldridge

Xiaohua Jin

Brittany DesRochers

Traci Bricker

Craig B Wilen

Juhi Bagaitkar

Ekaterina Loginicheva

Alexey Sergushichev

Darren Kreamalmeyer

Brian C Keller

Yan Zhao

Amal Kambal

Douglas R Green

Jennifer Martinez

Mary C Dinauer

Michael J Holtzman

Erika C Crouch

Wandy Beatty

Adrianus C M Boon

Hong Zhang

Gwendalyn J Randolph

Maxim N Artyomov

Herbert W Virgin

Affiliations

Soon will be listed here.

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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