tetano
Editor, Senior Moderator
Immunohorizons
. 2025 Nov 24;9(12):vlaf056.
doi: 10.1093/immhor/vlaf056. IL-13 protects epithelial cells from SARS-CoV-2 infection by inhibiting ACE2-mediated virus binding and cell entry
Vadim Pivniouk[SUP] 1 2 3 [/SUP], Oksana Pivniouk[SUP] 2 [/SUP], Jennifer L Uhrlaub[SUP] 4 [/SUP], Seongmin Hahn[SUP] 2 [/SUP], Allyson Molzahn[SUP] 5 [/SUP], Hiroki Kimura[SUP] 5 [/SUP], Mari Numata[SUP] 6 [/SUP], Hong Wei Chu[SUP] 6 [/SUP], Julie G Ledford[SUP] 1 2 3 [/SUP], Monica Kraft[SUP] 5 [/SUP], Janko Ž Nikolich[SUP] 3 4 7 [/SUP], Donata Vercelli[SUP] 1 2 3 8 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preferentially infects airway epithelial cells. This infection is mediated by the binding of SARS-CoV-2 spike (S) protein to ACE2 expressed on target cells. Patients with allergic (type-2) asthma have been reported to be less susceptible to coronavirus disease 2019 (COVID-19), but these effects are controversial and mechanistically unclear. We previously showed lower expression of ACE2 mRNA in airway epithelial cells from type-2 asthmatics compared to healthy donors. Moreover, we and others demonstrated that the type-2 cytokine interleukin 13 (IL-13) suppresses ACE2 expression and SARS-CoV-2 infection in human epithelial cells. To better understand the relationship between type-2 inflammation, ACE2 expression, and SARS-CoV-2 infection, we investigated the effects of IL-13 on critical steps of epithelial cell infection by SARS-CoV-2: S protein-mediated binding to ACE2 on epithelial cells, and ACE2-mediated SARS-CoV-2 entry into these cells. Recombinant IL-13 significantly inhibited both these processes. This inhibition appeared to be mediated by IL-13-induced suppression of ACE2 transcription because IL-13 failed to affect S protein-mediated viral entry into cells that express ACE2 under the control of an IL-13 unresponsive heterologous promoter. We propose that IL-13 protects epithelial cells from SARS-CoV-2 infection largely by inhibiting ACE2 expression and ACE2-mediated downstream events that allow the virus to access its cellular targets.
Keywords: ACE2; COVID-19; SARS-CoV-2; epithelial cells; type-2 inflammation.
. 2025 Nov 24;9(12):vlaf056.
doi: 10.1093/immhor/vlaf056. IL-13 protects epithelial cells from SARS-CoV-2 infection by inhibiting ACE2-mediated virus binding and cell entry
Vadim Pivniouk[SUP] 1 2 3 [/SUP], Oksana Pivniouk[SUP] 2 [/SUP], Jennifer L Uhrlaub[SUP] 4 [/SUP], Seongmin Hahn[SUP] 2 [/SUP], Allyson Molzahn[SUP] 5 [/SUP], Hiroki Kimura[SUP] 5 [/SUP], Mari Numata[SUP] 6 [/SUP], Hong Wei Chu[SUP] 6 [/SUP], Julie G Ledford[SUP] 1 2 3 [/SUP], Monica Kraft[SUP] 5 [/SUP], Janko Ž Nikolich[SUP] 3 4 7 [/SUP], Donata Vercelli[SUP] 1 2 3 8 [/SUP]
Affiliations
- PMID: 41285031
- DOI: 10.1093/immhor/vlaf056
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preferentially infects airway epithelial cells. This infection is mediated by the binding of SARS-CoV-2 spike (S) protein to ACE2 expressed on target cells. Patients with allergic (type-2) asthma have been reported to be less susceptible to coronavirus disease 2019 (COVID-19), but these effects are controversial and mechanistically unclear. We previously showed lower expression of ACE2 mRNA in airway epithelial cells from type-2 asthmatics compared to healthy donors. Moreover, we and others demonstrated that the type-2 cytokine interleukin 13 (IL-13) suppresses ACE2 expression and SARS-CoV-2 infection in human epithelial cells. To better understand the relationship between type-2 inflammation, ACE2 expression, and SARS-CoV-2 infection, we investigated the effects of IL-13 on critical steps of epithelial cell infection by SARS-CoV-2: S protein-mediated binding to ACE2 on epithelial cells, and ACE2-mediated SARS-CoV-2 entry into these cells. Recombinant IL-13 significantly inhibited both these processes. This inhibition appeared to be mediated by IL-13-induced suppression of ACE2 transcription because IL-13 failed to affect S protein-mediated viral entry into cells that express ACE2 under the control of an IL-13 unresponsive heterologous promoter. We propose that IL-13 protects epithelial cells from SARS-CoV-2 infection largely by inhibiting ACE2 expression and ACE2-mediated downstream events that allow the virus to access its cellular targets.
Keywords: ACE2; COVID-19; SARS-CoV-2; epithelial cells; type-2 inflammation.