Abstract
SummaryIn response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre-existing co-morbidities, correlating to incidence of severe COVID-19, are associated with chronic airway neutrophilia and examination of COVID-19 lung tissue revealed a series of epithelial pathologies associated with infiltration and activation of neutrophils. To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory response to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. We discovered that SARS-CoV-2 infection of the airway epithelium alone does not result in a notable release of pro-inflammatory cytokines, however in the presence of neutrophils, the inflammatory response is both polarized and significantly augmented, epithelial barrier integrity in impaired and viral load of the airway epithelium increased. This study reveals a key role for neutrophil-epithelial interactions in determining inflammation, infectivity, and outcomes in response to SARS-CoV-2 infection.HighlightsWe have developed a model to study neutrophil-epithelial interactions which better reflects the in vivo situation than monoculturesNeutrophils significantly augment SARS-CoV-2 mediated, pro-inflammatory cytokine release from the epithelium indicating a key interactionSARS-CoV-2 infection leads to a polarized inflammatory response in differentiated airway epitheliumDisruption of the epithelial barrier via addition of neutrophils or cytokines leads to increased infectionStudy reveals a key role for neutrophil-epithelial interactions in determining outcome/infectivity
Publisher
Cold Spring Harbor Laboratory
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