The interplay between SARS-CoV-2 infected airway epithelium and immune cells modulates regulatory/inflammatory signals

Veronica Bordoni; Giulia Matusali; Davide Mariotti; Manuela Antonioli; Eleonora Cimini; Alessandra Sacchi; Eleonora Tartaglia; Rita Casetti; Germana Grassi; Stefania Notari; Concetta Castilletti; Gian Maria Fimia; Maria Rosaria Capobianchi; Giuseppe Ippolito; Chiara Agrati

doi:10.1016/j.isci.2022.103854

The interplay between SARS-CoV-2 infected airway epithelium and immune cells modulates regulatory/inflammatory signals

iScience. 2022 Feb 18;25(2):103854. doi: 10.1016/j.isci.2022.103854. Epub 2022 Jan 31.

Authors

Veronica Bordoni¹, Giulia Matusali¹, Davide Mariotti¹, Manuela Antonioli¹, Eleonora Cimini¹, Alessandra Sacchi¹, Eleonora Tartaglia¹, Rita Casetti¹, Germana Grassi¹, Stefania Notari¹, Concetta Castilletti¹, Gian Maria Fimia^{1

2}, Maria Rosaria Capobianchi¹, Giuseppe Ippolito¹, Chiara Agrati¹

Affiliations

¹ National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, Via Portuense, 292, Rome 00149, Italy.
² Department of Molecular Medicine, University of Rome "Sapienza", Rome, Italy.

Abstract

To assess the cross-talk between immune cells and respiratory tract during SARS-CoV-2 infection, we analyzed the relationships between the inflammatory response induced by SARS-CoV-2 replication and immune cells phenotype in a reconstituted organotypic human airway epithelium (HAE). The results indicated that immune cells failed to inhibit SARS-CoV-2 replication in the HAE model. In contrast, immune cells strongly affected the inflammatory profile induced by SARS-CoV-2 infection, dampening the production of several immunoregulatory/inflammatory signals (e.g., IL-35, IL-27, and IL-34). Moreover, these mediators were found inversely correlated with innate immune cell frequency (NK and γδ T cells) and directly with CD8 T cells. The enriched signals associated with NK and CD8 T cells highlighted the modulation of pathways induced by SARS-CoV-2 infected HAE. These findings are useful to depict the cell-cell communication mechanisms necessary to develop novel therapeutic strategies aimed to promote an effective immune response.

Keywords: Immunology; Virology.