Journal article
Complement is primarily activated in the lung in a mouse model of severe COVID-19
iScience, Vol.28(3), 111930
03/2025
DOI: 10.1016/j.isci.2025.111930
PMCID: PMC11875145
PMID: 40034849
Abstract
Summary
In vitro studies and observational human disease data suggest the complement system contributes to SARS-CoV-2 pathogenesis, although how complement dysregulation develops in severe COVID-19 is unknown. Here, using a mouse-adapted SARS-CoV-2 virus (SARS2-N501YMA30) and a mouse model of COVID-19, we identify significant serologic and pulmonary complement activation post-infection. We observed C3 activation in airway and alveolar epithelia, and pulmonary vascular endothelia. Our evidence suggests the alternative pathway is the primary route of complement activation, however, components of both the alternative and classical pathways are produced locally by respiratory epithelial cells following infection, and increased in primary cultures of human airway epithelia following cytokine and SARS-CoV-2 exposure. This tissue-specific complement response appears to precede lung injury and inflammation. Our results suggest that complement activation is a defining feature of severe COVID-19 in mice, agreeing with previous publications, and provide the basis for further investigation into the role of complement in COVID-19.
Details
- Title: Subtitle
- Complement is primarily activated in the lung in a mouse model of severe COVID-19
- Creators
- Peter J. SzachowiczChristine Wohlford-LenaneCobey J. HeinenShreya GhimireAndrew ThurmanBiyun XueTimothy J. BolyAbhishek VermaLeila MašinoviĆJennifer R. BermickTayyab RehmanStanley PerlmanDavid K. MeyerholzAlejandro A. PezzuloYuzhou ZhangRichard J.H. SmithPaul B. McCray
- Resource Type
- Journal article
- Publication Details
- iScience, Vol.28(3), 111930
- DOI
- 10.1016/j.isci.2025.111930
- PMID
- 40034849
- PMCID
- PMC11875145
- NLM abbreviation
- iScience
- ISSN
- 2589-0042
- eISSN
- 2589-0042
- Publisher
- CELL PRESS
- Grant note
- National Institutes of Health (NIH): P01 AI-060699 Center for Gene Therapy of Cystic Fibrosis: P30 DK-54759 University of Iowa Carver College of Medicine COVID-19 Pilot GrantTully Family FoundationRoy J. Carver Charitable TrustCarver College of Medicine: COVID-19 NHLBI: 1R01HL163024
We would like to thank Paul Morgan, Wioleta Zelek, Ron Taylor, Santiago Rodriguez de Cordoba, and Matthew Pickering for the sharing of reagents, experimental assistance, and helpful discussions that contributed to this manuscript. We would like to thank the Tully family for their support. This work was supported with funding from National Institutes of Health (NIH) (P01 AI-060699) , the Center for Gene Therapy of Cystic Fibrosis (P30 DK-54759) (P.B.M.) , the University of Iowa Carver College of Medicine COVID-19 Pilot Grant, and the Tully Family Foundation. P.B.M. is supported by the Roy J. Carver Charitable Trust. Carver College of Medicine COVID-19 Grant (P.B.M. and A.P.) , and NHLBI 1R01HL163024 (A.P.) . Role of the funding source: The funders of this original research had no role in the study design, writing of the report, interpretation of data, or the decision to submit the paper for publication.
- Language
- English
- Electronic publication date
- 02/2025
- Date published
- 03/2025
- Academic Unit
- Microbiology and Immunology; Pathology; Neonatology; Otolaryngology; Infectious Disease (Pediatrics); Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pulmonary Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984785479102771
Metrics
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