RT Journal Article
SR Electronic
T1 Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.09.455472
DO 10.1101/2021.08.09.455472
A1 BA Calvert
A1 EJ Quiroz
A1 Z Lorenzana
A1 N Doan
A1 S Kim
A1 CN Senger
A1 WD Wallace
A1 MP Salomon
A1 J Henley
A1 AL Ryan
YR 2022
UL http://biorxiv.org/content/early/2022/06/06/2021.08.09.455472.abstract
AB In 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. Furthermore, examination of COVID-19 explanted lung tissue revealed a series of epithelial pathologies associated with the infiltration and activation of neutrophils, indicating neutrophil activity in response to SARS- CoV-2 infection. To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory responses to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. SARS-CoV-2 infection of the airway epithelium alone does not result in a notable pro-inflammatory response from the epithelium. The addition of neutrophils induces the release of proinflammatory cytokines and stimulates a significantly augmented pro-inflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory response is polarized with differential release from the apical and basolateral side of the epithelium. Additionally, the integrity of the epithelial barrier is impaired with notable epithelial damage and infection of basal stem cells. This study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity in response to SARS-CoV-2 infection.Competing Interest StatementThe authors have declared no competing interest.