ArticleCell host & microbe2023
An epithelial-immune circuit amplifies inflammasome and IL-6 responses to SARS-CoV-2.
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Article in Cell host & microbe, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51citing papers in PubMed
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51 citing papers in PubMed, 69 citations in OpenAlex.
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- SARS-CoV-2 infection induces pro-fibrotic and pro-thrombotic foam cell formation.Nature microbiology · 2025Article
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- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Artificial intelligence-powered prediction of AIM-2 inflammasome sequences using transformers and graph attention networks in periodontal inflammation.Scientific reports · 2025Article
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Authors and funding
18 authors at 3 institutions in 1 country.
Katherine C BarnettDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yuying XieDepartment of Computational Mathematics, Science and Engineering, Michigan State University, East Lansing, MI 48824, USA; Department of Statistics and Probability, Michigan State University, East Lansing, MI 48824, USA.
Takanori AsakuraMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Dingka SongDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kaixin LiangDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Oral and Craniofacial Biomedicine Program, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sharon A Taft-BenzDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Haitao GuoDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Shuangshuang YangDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kenichi OkudaMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Rodney C GilmoreMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jennifer F LoomeDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Thomas H Oguin IiiDuke Human Vaccine Institute, Durham, NC 27701, USA.
Gregory D SempowskiDuke Human Vaccine Institute, Durham, NC 27701, USA.
Scott H RandellDepartment of Statistics and Probability, Michigan State University, East Lansing, MI 48824, USA.
Mark T HeiseDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yu Leo LeiDepartment of Periodontics and Oral Medicine, Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48104, USA; Department of Otolaryngology-Head and Neck Surgery, Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Richard C BoucherMarsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jenny P-Y TingDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: jenny_ting@med.unc.edu.
University of North Carolina at Chapel Hill · USMichigan State University · USUniversity of Michigan · US
Funding
Unlocking Zika Virus Immune Control and Pathogenesis with the Collaborative CrossU19AI100625 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PARDO-MANUEL DE VILLENA, FERNANDO · 2012 to 2021
$36.6MVector CoreP30DK065988 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Martina Gentzsch · 2004 to 2026
$26.5MThe Biophysics of Mucus Hydration and Adhesion/CohesionP01HL108808 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUBINSTEIN, MICHAEL · 2012 to 2021
$23.9MRegional Biocontainment Laboratory (RBL)UC6AI058607 · NIAID · DUKE UNIVERSITY · PI WILLIAMS, R SANDERS · 2003 to 2005
$16.3MIntracellular Innate Immune Receptors in Cancer Suppression and ImmunotherapyR35CA232109 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TING, JENNY P · 2019 to 2025
$6.4MMolecular and Functional Analysis of NLR Family MembersR01AI029564 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jenny P Ting · 1991 to 2026
$6.0MMicro-Particle Delivery of a Potent Intracellular Adjuvant for a Universal Flu VaccineR01AI141333 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BACHELDER, ERIC, TING, JENNY P · 2019 to 2023
$5.9MCANCER CELL BIOLOGY TRAINING PROGRAMT32CA071341 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHANNING J. DER, Yuliya Pylayeva-Gupta · 1996 to 2026
$5.0MSynthesis of Effective and Safe Mucolytics for Pulmonary DiseaseUH3HL123645 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2016 to 2018
$4.6MRestoring the Immunogenicity of Head and Neck CancerR01DE026728 · NIDCR · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Yu Leo Lei, James J. Moon · 2018 to 2026
$4.3MRobust Immuno-prevention Strategies for High-Risk Oral Epithelial DysplasiaU01DE029255 · NIDCR · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BRENNER, JOHN CHADWICK, LEI, YU LEO · 2019 to 2021
$4.2MGenetic Analysis of COVID-19 Susceptibility and Resistance Determinants in the Collaborative CrossR01AI157253 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BARIC, RALPH S, HEISE, MARK T · 2020 to 2024
$3.8MNCI NIH HHS R35 CA232109NCI NIH HHS T32 CA071341NHLBI NIH HHS P01 HL108808NHLBI NIH HHS R01 HL136961NHLBI NIH HHS UH3 HL123645NIAID NIH HHS R01 AI029564NIAID NIH HHS R01 AI141333NIAID NIH HHS R01 AI157253NIAID NIH HHS R01 AI158314NIAID NIH HHS R37 AI029564NIAID NIH HHS R56 AI029564NIAID NIH HHS R56 AI158314NIAID NIH HHS U19 AI100625NIAID NIH HHS UC6 AI058607NIDCR NIH HHS R01 DE026728NIDCR NIH HHS R01 DE031951NIDCR NIH HHS U01 DE029255NIDDK NIH HHS P30 DK065988NIEHS NIH HHS R01 ES032643
Abstract
Elevated levels of cytokines IL-1β and IL-6 are associated with severe COVID-19. Investigating the underlying mechanisms, we find that while primary human airway epithelia (HAE) have functional inflammasomes and support SARS-CoV-2 replication, they are not the source of IL-1β released upon infection. In leukocytes, the SARS-CoV-2 E protein upregulates inflammasome gene transcription via TLR2 to prime, but not activate, inflammasomes. SARS-CoV-2-infected HAE supply a second signal, which includes genomic and mitochondrial DNA, to stimulate leukocyte IL-1β release. Nuclease treatment, STING, and caspase-1 inhibition but not NLRP3 inhibition blocked leukocyte IL-1β release. After release, IL-1β stimulates IL-6 secretion from HAE. Therefore, infection alone does not increase IL-1β secretion by either cell type. Rather, bi-directional interactions between the SARS-CoV-2-infected epithelium and immune bystanders stimulates both IL-1β and IL-6, creating a pro-inflammatory cytokine circuit. Consistent with these observations, patient autopsy lungs show elevated myeloid inflammasome gene signatures in severe COVID-19.
Indexed as
COVID-19InflammasomesCytokinesHumansInterleukin-1betaInterleukin-6NLR Family, Pyrin Domain-Containing 3 ProteinSARS-CoV-2CytokinesInflammasomesInterleukin-1betaInterleukin-6NLR Family, Pyrin Domain-Containing 3 ProteinAIM2IL-1βIL-6inflammasomeNLRP1NLRP3SARS-CoV-2STINGTLR2
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