ArticleThe Journal of allergy and clinical immunology2021
C5aR inhibition of nonimmune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2-infected primary human airway epithelia.
Article in The Journal of allergy and clinical immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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48 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
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- Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variant.Molecular therapy. Nucleic acids · 2025Article
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- Resistance to complement-mediated lysis of parainfluenza virus 5-infected cells is acquired after transition from acute to persistent infection.Journal of virology · 2025Article
- Methods and Models for StudyingInternational journal of molecular sciences · 2024Review
- Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.Developmental cell · 2024Article
- Pathophysiological dynamics in the contact, coagulation, and complement systems during sepsis: Potential targets for nafamostat mesilate.Journal of intensive medicine · 2024Review
- A Histological Analysis and Detection of Complement Regulatory Protein CD55 in SARS-CoV-2 Infected Lungs.Life (Basel, Switzerland) · 2024Article
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- A predominately pulmonary activation of complement in a mouse model of severe COVID-19.bioRxiv : the preprint server for biology · 2024Article
- Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies.The EMBO journal · 2024Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundExcessive inflammation triggered by a hitherto undescribed mechanism is a hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and is associated with enhanced pathogenicity and mortality.
objectiveComplement hyperactivation promotes lung injury and was observed in patients suffering from Middle East respiratory syndrome-related coronavirus, SARS-CoV-1, and SARS-CoV-2 infections. Therefore, we investigated the very first interactions of primary human airway epithelial cells on exposure to SARS-CoV-2 in terms of complement component 3 (C3)-mediated effects.
methodsFor this, we used highly differentiated primary human 3-dimensional tissue models infected with SARS-CoV-2 patient isolates. On infection, viral load, viral infectivity, intracellular complement activation, inflammatory mechanisms, and tissue destruction were analyzed by real-time RT-PCR, high content screening, plaque assays, luminex analyses, and transepithelial electrical resistance measurements.
resultsHere, we show that primary normal human bronchial and small airway epithelial cells respond to SARS-CoV-2 infection by an inflated local C3 mobilization. SARS-CoV-2 infection resulted in exaggerated intracellular complement activation and destruction of the epithelial integrity in monolayer cultures of primary human airway cells and highly differentiated, pseudostratified, mucus-producing, ciliated respiratory tissue models. SARS-CoV-2-infected 3-dimensional cultures secreted significantly higher levels of C3a and the proinflammatory cytokines IL-6, monocyte chemoattractant protein 1, IL-1α, and RANTES.
conclusionsCrucially, we illustrate here for the first time that targeting the anaphylotoxin receptors C3a receptor and C5a receptor in nonimmune respiratory cells can prevent intrinsic lung inflammation and tissue damage. This opens up the exciting possibility in the treatment of COVID-19.
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