Rhinovirus triggers distinct host responses through differential engagement of epithelial innate immune signaling - Donor information

Description

Donor metadata of primary human nasal epithelial cells used in the study. In this study: We used single cell sequencing of the organotypic air-liquid interface culture model to reveal innate defense responses of the human nasal epithelium to rhinovirus, the most frequent cause of common colds and a major cause of serious respiratory illness in high-risk groups (e.g. smokers and asthmatics). We found that the epithelial interferon response restricts RV infection to <2% of cells. However, inhibiting the interferon response by blocking IRF3 activation increases the proportion of infected cells to >30%, and leads to a distinct NFKB- and NLRP1-dependent pro-inflammatory response, with production of neutrophil-attracting chemokines, increased mucus, and IL-1b. Inhibiting both IRF3 and NFKB increases cell death, ER stress and squamous metaplasia. Overall, this study demonstrates how epithelial innate immune signaling impacts RV-induced inflammation and reveals potential therapeutic targets.

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Institutions

• Yale University School of Medicine

  CT, New Haven

Categories

Funders

• Rita Allen Foundation

  New Jersey, United States
• National Institute of Allergy and Infectious Diseases

  Maryland, United States
• Yale University

  Connecticut, United States

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