Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells

被引：11

作者：

Calvert, Ben A. A. ^{[1
,2
]}

Quiroz, Erik J. J. ^{[1
,2
,3
]}

Lorenzana, Zareeb ^{[1
]}

Doan, Ngan ^{[1
]}

Kim, Seongjae ^{[4
]}

Senger, Christiana N. N. ^{[1
]}

Anders, Jeffrey J. J. ^{[2
]}

Wallace, Wiliam D. D. ^{[5
]}

Salomon, Matthew P. P. ^{[6
]}

Henley, Jill ^{[6
]}

Ryan, Amy L. L. ^{[1
,2
,3
]}

机构：

[1] Univ Southern Calif, Hastings Ctr Pulm Res, Dept Med, Div Pulm Crit Care & Sleep Med, Los Angeles, CA 90007 USA

[2] Univ Iowa, Carver Coll Med, Dept Anat & Cell Biol, Iowa, IA 52242 USA

[3] Univ Southern Calif, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90007 USA

[4] Salk Inst Biol Studies, La Jolla, CA USA

[5] Univ Southern Calif, Dept Pathol, Los Angeles, CA USA

[6] Univ Southern Calif, Dept Med, Los Angeles, CA USA

来源：

FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷

关键词：

airway epithelium; cell-cell interactions; cytokines; inflammation; neutrophils; viral infection; COVID-19; CHEMOTACTIC FACTOR; CYTOKINE; INTERLEUKIN-8; EXPRESSION;

D O I：

10.3389/fimmu.2023.1112870

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

IntroductionIn 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 to 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. MethodsTo 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. This model was infected with live SARS-CoV-2 virus the epithelial response to infection was evaluated. ResultsSARS-CoV-2 infection of 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 proinflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory responses are 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. ConclusionsThis study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity.

引用

页数：16

共 70 条

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