The lung employs an intrinsic surfactant-mediated inflammatory response for viral defense.

Abstract

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes an acute respiratory distress syndrome (ARDS) that resembles surfactant deficient RDS. Using a novel multi-cell type, human induced pluripotent stem cell (hiPSC)-derived lung organoid (LO) system, validated against primary lung cells, we found that inflammatory cytokine/chemokine production and interferon (IFN) responses are dynamically regulated autonomously within the lung following SARS-CoV-2 infection, an intrinsic defense mechanism mediated by surfactant proteins (SP). Single cell RNA sequencing revealed broad infectability of most lung cell types through canonical (ACE2) and non-canonical (endocytotic) viral entry routes. SARS-CoV-2 triggers rapid apoptosis, impairing viral dissemination. In the absence of surfactant protein B (SP-B), resistance to infection was impaired and cytokine/chemokine production and IFN responses were modulated. Exogenous surfactant, recombinant SP-B, or genomic correction of the SP-B deletion restored resistance to SARS-CoV-2 and improved viability.

• Authors: Sandra L Leibel, Rachael N McVicar, Rabi Murad, Elizabeth M Kwong, Alex E Clark, Asuka Alvarado, Bethany A Grimmig, Ruslan Nuryyev, Randee E Young, Jamie Casey Lee, Weiqi Peng, Yanfang Peipei Zhu, Eric Griffis, Cameron J Nowell, Kang Liu, Brian James, Suzie Alarcon, Atul Malhotra, Linden J Gearing, Paul J Hertzog, Cheska Marie Galapate, Koen M O Galenkamp, Cosimo Commisso, Davey M Smith, Xin Sun, Aaron F Carlin, Ben A Croker, Evan Y Snyder
• Journal: bioRxiv : the preprint server for biology (bioRxiv) (Jan 27 2023) United States
• PMID: 36747824 (Publication Type: Preprint)