ArticleCell host & microbe2016
Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis.
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Article in Cell host & microbe, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65citing papers in PubMed
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65 citing papers in PubMed, 99 citations in OpenAlex.
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Autophagy functions in lung macrophages and dendritic cells to regulate allergen-dependent inflammatory responses.Autophagy · 2026Article
- Pathogenic variants in the autophagy-tethering factor EPG5 drive neurodegeneration through mitochondrial dysfunction and innate immune activation.Nature communications · 2026Article
- Progressive neuroinflammation and deficits in motor function in a mouse model with an Epg5 pathogenic variant of Vici syndrome.Experimental & molecular medicine · 2026Article
- ATG-3 limits Orsay virus infection in C. elegans and regulates collagen pathways.PLoS pathogens · 2025Article
- Article
- Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway.Cellular & molecular immunology · 2024Article
- Context-dependent roles for autophagy in myeloid cells in tumor progression.bioRxiv : the preprint server for biology · 2024Article
- FEAR antiviral response pathway is independent of interferons and countered by poxvirus proteins.Nature microbiology · 2024Article
- Autophagy promotes efficient T cell responses to restrict high-dose Mycobacterium tuberculosis infection in mice.Nature microbiology · 2024Article
- Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits.PLoS biology · 2024Article
- Altered Expression of Autophagy Biomarkers in Hippocampal Neurons in a Multiple Sclerosis Animal Model.International journal of molecular sciences · 2023Article
- Constitutively active autophagy in macrophages dampens inflammation through metabolic and post-transcriptional regulation of cytokine production.Cell reports · 2023Article
- Autophagy restricts Mycobacterium tuberculosis during acute infection in mice.Nature microbiology · 2023Article
- Myeloid autophagy genes protect mice against fatal TNF- and LPS-induced cytokine storm syndromes.Autophagy · 2023Article
- Atg8ylation as a host-protective mechanism againstFrontiers in tuberculosis · 2023Article
- Role of endoplasmic reticulum autophagy in acute lung injury.Frontiers in immunology · 2023Review
- CD44a functions as a regulator of p53 signaling, apoptosis and autophagy in the antibacterial immune response.Communications biology · 2022Article
- A guide to membrane atg8ylation and autophagy with reflections on immunity.The Journal of cell biology · 2022Article
- Intestinal antiviral signaling is controlled by autophagy geneAutophagy · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 6 institutions in 3 countries.
Qun LuDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Christine C YokoyamaDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jesse W WilliamsDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Megan T BaldridgeDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Xiaohua JinDepartment of Internal Medicine (Pulmonary and Critical Care Medicine), Washington University School of Medicine, St. Louis, MO 63110, USA.
Brittany DesRochersDepartment of Internal Medicine (Pulmonary and Critical Care Medicine), Washington University School of Medicine, St. Louis, MO 63110, USA.
Traci BrickerDepartment of Internal Medicine (Pulmonary and Critical Care Medicine), Washington University School of Medicine, St. Louis, MO 63110, USA.
Craig B WilenDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Juhi BagaitkarDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pediatrics (Hematology/Oncology), Washington University School of Medicine, St. Louis, MO 63110, USA.
Ekaterina LoginichevaDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Alexey SergushichevDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Computer Technologies Department, ITMO University, St. Petersburg 197101, Russia.
Darren KreamalmeyerDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Brian C KellerDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Internal Medicine (Pulmonary and Critical Care Medicine), Washington University School of Medicine, St. Louis, MO 63110, USA.
Yan ZhaoState Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Amal KambalDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Douglas R GreenDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jennifer MartinezImmunity, Inflammation, and Disease Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, NC 27703, USA.
Mary C DinauerDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pediatrics (Hematology/Oncology), Washington University School of Medicine, St. Louis, MO 63110, USA.
Michael J HoltzmanDepartment of Internal Medicine (Pulmonary and Critical Care Medicine), Washington University School of Medicine, St. Louis, MO 63110, USA.
Erika C CrouchDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wandy BeattyDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Adrianus C M BoonDepartment of Internal Medicine (Pulmonary and Critical Care Medicine), Washington University School of Medicine, St. Louis, MO 63110, USA.
Hong ZhangState Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Gwendalyn J RandolphDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Maxim N ArtyomovDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Herbert W VirginDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: virgin@wustl.edu.
Washington University in St. Louis · USChinese Academy of Sciences · CNInstitute of Biophysics · CNITMO University · RUNational Institutes of Health · USSt. Jude Children's Research Hospital · US
Funding
Genetic and Pathway Analysis CoreU19AI109725 · NIAID · WASHINGTON UNIVERSITY · PI ALLEN, PAUL M · 2014 to 2018
$32.7MTissue and Cell Processing CoreU19AI070489 · NIAID · WASHINGTON UNIVERSITY · PI HOLTZMAN, MICHAEL J · 2006 to 2016
$17.9MPRINCIPLES IN PULMONARY RESEARCHT32HL007317 · NHLBI · WASHINGTON UNIVERSITY · PI Steven Brody, Michael J Holtzman · 1985 to 2026
$16.1MDIABETES &RELATED METABOLIC DISEASEST32DK007120 · NIDDK · WASHINGTON UNIVERSITY · PI MARCO COLONNA, Maria Sara Remedi · 1986 to 2026
$15.7MTRAINING PROGRAM IN IMMUNOLOGY AND IMMUNOGENETICST32AI007163 · NIAID · WASHINGTON UNIVERSITY · PI Kenneth M Murphy, Kodi S Ravichandran · 1985 to 2026
$14.8MTRAINING IN THE IMMUNOBIOLOGY AND MOLECULAR CELL BIOLOGY OF CANCERT32CA009547 · NCI · WASHINGTON UNIVERSITY · PI ROBERT DAVID SCHREIBER · 1986 to 2026
$12.1MCharacterization of the molecular mechanisms of LC3-associated phagocytosis and its role in disease pathogenesisZIAES103286 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MARTINEZ, JENNIFER · 2015 to 2021
$9.2MNon-canonical functions of autophagy proteinsR01AI040646 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI GREEN, DOUGLAS R. · 1997 to 2023
$8.6MDifferentiation/migratory fate of monocyte-derived cellsR01AI049653 · NIAID · WASHINGTON UNIVERSITY · PI Gwendalyn J Randolph · 2000 to 2026
$4.6MDIFFERENTIATION AND FUNCTION OF MONOCYTES AND MACROPHAGESR37AI049653 · NIAID · WASHINGTON UNIVERSITY · PI RANDOLPH, GWENDALYN J · 2016 to 2025
$4.3MCELL BIOLOGIC APPROACHES TO DIABETES RESEARCHT32DK007296 · NIDDK · WASHINGTON UNIVERSITY · PI COLONNA, MARCO · 1986 to 2014
$3.3MIL-33 AND EXCESS MUCUS PRODUCTIONR01HL121791 · NHLBI · WASHINGTON UNIVERSITY · PI HOLTZMAN, MICHAEL J · 2014 to 2017
$1.9MHoward Hughes Medical InstituteIntramural NIH HHS Z99 ES999999Intramural NIH HHS ZIA ES103286NCI NIH HHS T32 CA009547NCI NIH HHS T32CA009547NHLBI NIH HHS R01 HL121791NHLBI NIH HHS R01HL121791NHLBI NIH HHS T32 HL007317NHLBI NIH HHS T32HL07317NIAID NIH HHS AI049653NIAID NIH HHS R01 AI040646NIAID NIH HHS R01 AI049653NIAID NIH HHS R01 AI111605NIAID NIH HHS R01AI111605NIAID NIH HHS R37 AI049653NIAID NIH HHS T32 AI007163NIAID NIH HHS T32AI007163NIAID NIH HHS U19 AI070489NIAID NIH HHS U19AI070489NIAID NIH HHS U19 AI109725NIAID NIH HHS U19AI109725NIDDK NIH HHS T32 DK007120NIDDK NIH HHS T32 DK007296NIDDK NIH HHS T32DK7296
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.
Indexed as
Immunity, InnateAnimalsAutophagy-Related Protein 7Autophagy-Related ProteinsHomeostasisHumansInfluenza A Virus, H1N1 SubtypeInfluenza, HumanMacrophagesMiceMice, KnockoutMicrotubule-Associated ProteinsPneumoniaProteinsVesicular Transport ProteinsAtg14 protein, mouseAtg7 protein, mouseAutophagy-Related Protein 7Autophagy-Related ProteinsEpg5 protein, mouseMicrotubule-Associated ProteinsProteinsVesicular Transport Proteins
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