García-Bernalt Diego J,
Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia. iScience. 2023;26(8):107374
This work is partially supported by NIAID grants U19AI142733 (K.P.) and U19AI135972 (A.G.-S.); R01AI141609 (A.W.); R01AI160706 (M.S.); by NIDDK grant R01DK130425 (M.S.); by NCI grants P30 CA034196 (K.P.) and U54CA260560 (A.G.-S.). By CRIPT (Center for Research on Influenza Pathogenesis and Transmission), and NIAID funded Center of Excellence for Influenza Research and Response (CEIRR, contract number 75N93021C00014) to A.G.-S.
The COVID-19 pandemic continues to be a health crisis with major unmet medical needs. The early responses from airway epithelial cells, the first target of the virus regulating the progression toward severe disease, are not fully understood. Primary human air-liquid interface cultures representing the broncho-alveolar epithelia were used to study the kinetics and dynamics of SARS-CoV-2 variants infection. The infection measured by nucleoprotein expression, was a late event appearing between day 4-6 post infection for Wuhan-like virus. Other variants demonstrated increasingly accelerated timelines of infection. All variants triggered similar transcriptional signatures, an "early" inflammatory/immune signature preceding a "late" type I/III IFN, but differences in the quality and kinetics were found, consistent with the timing of nucleoprotein expression. Response to virus was spatially organized: CSF3 expression in basal cells and CCL20 in apical cells. Thus, SARS-CoV-2 virus triggers specific responses modulated over time to engage different arms of immune response.