C5aR inhibition of nonimmune cells suppresses inflammation and maintains epithelial integrity in SARS-CoV-2–infected primary human airway epithelia

• DOI: 10.1016/j.jaci.2021.03.038
• Publication Date: 2021-04-21T00:41:18Z
• Authors: Wilfried Posch; Jonathan Vosper; Asma Noureen; Viktoria Zaderer; Christina Witting; Giulia Bertacchi; Ronald Gstir; Przemyslaw A. Fil...; Günther K. Bonn; Lukas A. Huber; Rosa Bellmann-Weiler; Cornelia Lass-Flörl; Doris Wilflingseder
• Keywords: Inflammation; 0303 health sciences; SARS-CoV-2; COVID-19; Bronchi; Epithelial Cells; Complement C3; Respiratory Mucosa; Cell Line; 3. Good health; 03 medical and health sciences; Cytokines; Humans; Covid-19; Complement Activation; Receptor, Anaphylatoxin C5a

BackgroundExcessive inflammation triggered by a hitherto undescribed mechanism is hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and associated with enhanced pathogenicity mortality.ObjectiveComplement hyperactivation promotes lung injury was observed in patients suffering from Middle East syndrome-related coronavirus, SARS-CoV-1, SARS-CoV-2 infections. Therefore, we investigated the very first interactions primary human airway epithelial cells on exposure to terms complement component 3 (C3)-mediated effects.MethodsFor this, used highly differentiated 3-dimensional tissue models infected patient isolates. On infection, viral load, infectivity, intracellular activation, inflammatory mechanisms, destruction were analyzed real-time RT-PCR, high content screening, plaque assays, luminex analyses, transepithelial electrical resistance measurements.ResultsHere, show that normal bronchial small respond infection an inflated local C3 mobilization. resulted exaggerated activation integrity monolayer cultures differentiated, pseudostratified, mucus-producing, ciliated models. SARS-CoV-2–infected secreted significantly higher levels C3a proinflammatory cytokines IL-6, monocyte chemoattractant protein 1, IL-1α, RANTES.ConclusionsCrucially, illustrate here for time targeting anaphylotoxin receptors receptor C5a nonimmune can prevent intrinsic damage. This opens up exciting possibility treatment COVID-19. Excessive mortality. Complement effects. For measurements. Here, RANTES. Crucially,