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

To assess the cross-talk between immune cells and respiratory tract during SARSCoV-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 gamma delta 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.

Automated summary

This study examines the cross-talk between immune cells and the respiratory tract during SARS-CoV-2 infection. The results show that while immune cells cannot inhibit the replication of the virus, they strongly affect the inflammatory profile induced by the infection. The frequency of NK and γδT cells is negatively correlated with the production of immunoregulatory/inflammatory signals, while CD8 T cells are positively correlated.