The pro-inflammatory response to influenza A virus infection is fueled by endothelial cells

Lisa Bauer*, Laurine C. Rijsbergen, Lonneke Leijten, Feline Fw Benavides, Danny Noack, Mart M. Lamers, Bart L. Haagmans, Rory D. de Vries, Rik L. de Swart, Debby van Riel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

Morbidity and mortality from influenza are associated with high levels of systemic inflammation. Endothelial cells play a key role in systemic inflammatory responses during severe influenza A virus (IAV) infections, despite being rarely infected in humans. How endothelial cells contribute to systemic inflammatory responses is unclear. Here, we developed a transwell system in which airway organoid-derived differentiated human lung epithelial cells were co-cultured with primary human lung microvascular endothelial cells (LMECs). We compared the susceptibility of LMECs to pandemic H1N1 virus and recent seasonal H1N1 and H3N2 viruses and assessed the associated pro-inflammatory responses. Despite the detection of IAV nucleoprotein in LMEC mono-cultures, there was no evidence for productive infection. In epithelial-endothelial co-cultures, abundant IAV infection of epithelial cells resulted in the breakdown of the epithelial barrier, but infection of LMECs was rarely detected. We observed a significantly higher secretion of pro-inflammatory cytokines in LMECs when co-cultured with IAV-infected epithelial cells than LMEC mono-cultures exposed to IAV. Taken together, our data show that LMECs are abortively infected by IAV but can fuel the inflammatory response.

Original languageEnglish
Article numbere202201837
Number of pages11
JournalLife Science Alliance
Volume6
Issue number7
DOIs
Publication statusPublished - Jul 2023

Bibliographical note

Funding Information:
D van Riel is supported by fellowships from the Netherlands Organization for Scientific Research (VIDI contract 91718308) and a EUR fellowship.

Publisher Copyright:
© 2023 Bauer et al.

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