Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia.

Authors

Diana Cadena, The Jackson LaboratoryFollow
Sonia Jangra
Marina Yurieva, The Jackson LaboratoryFollow
Jan Martinek, The Jackson LaboratoryFollow
Megan Callender, The Jackson LaboratoryFollow
Matthew Coxe, The Jackson LaboratoryFollow
Angela Choi
Juan García-Bernalt Diego
Jianan Lin, The Jackson LaboratoryFollow
Te-Chia Wu, The Jackson LaboratoryFollow
Florentina Marches, The Jackson LaboratoryFollow
Damien Chaussabel, The Jackson LaboratoryFollow
Peter Yu
Andrew Salner
Gabrielle Aucello, The Jackson Laboratory
Jonathan Koff
Briana Hudson
Sarah E Church
Kara Gorman
Esperanza Anguiano
Adolfo García-Sastre
Adam Williams, The Jackson LaboratoryFollow
Michael Schotsaert
Karolina Palucka, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

8-18-2023

Original Citation

Cadena D, Jangra S, Yurieva M, Martinek J, Callender M, Coxe M, Choi A, García-Bernalt Diego J, Lin J, Wu T, Marches F, Chaussabel D, Yu P, Salner A, Aucello G, Koff J, Hudson B, Church S, Gorman K, Anguiano E, García-Sastre A, Williams A, Schotsaert M, Palucka K. Spatiotemporally organized immunomodulatory response to SARS-CoV-2 virus in primary human broncho-alveolar epithelia. iScience. 2023;26(8):107374

Keywords

JGM

JAX Source

iScience. 2023;26(8):107374

ISSN

2589-0042

PMID

37520727

DOI

https://doi.org/10.1016/j.isci.2023.107374

Grant

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.

Abstract

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.

Comments

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).