IL-13 protects epithelial cells from SARS-CoV-2 infection by inhibiting early ACE2-mediated events

Abstract Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) infection is mediated by binding of viral spike (S) protein to membrane ACE2 on host epithelial cells, preferentially in the airway. Asthmatics with type 2 (T2) inflammation are reportedly less susceptible disease, but underlying mechanisms unclear. We recently showed that ACE2expression decreased airway cells from T2 asthmatics and consistently suppressed human primary cultured IL-13 (PMID: 32422146). To dissect IL-13/SARS-CoV-2 interactions, we assessed effects discrete events SARS-CoV-2 infection. S1 green monkey kidney Vero E6, lung Calu-3 HEK293T stably transfected ACE2(hACE2-HEK293T) was measured flow cytometry His-tagged protein. S protein-mediated entry into E6 hACE2-HEK293T using protein-pseudotyped lentiviral particles carrying a GFP reporter. ACE2transcription RT-qPCR. expression hACE2-HTK293T evaluated cytometry. USA-WA1/2020 used infect cells. strongly inhibited binding, cell entry, SARS-CoV-2. These resulted at least part IL-13-dependent inhibition because did not affect to, lentivirus into, do downregulate response IL-13. suggest protects inhibiting early ACE2-mediated events. Supported grant NIAID: U19 AI125357