Neutrophils play a major role in the destruction of the olfactory epithelium during SARS-CoV-2 infection in hamsters - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 Accéder directement au contenu
Article Dans Une Revue Cellular and Molecular Life Sciences Année : 2022

Neutrophils play a major role in the destruction of the olfactory epithelium during SARS-CoV-2 infection in hamsters

Résumé

The loss of smell (anosmia) related to SARS-CoV-2 infection is one of the most common symptoms of COVID-19. Olfaction starts in the olfactory epithelium mainly composed of olfactory sensory neurons surrounded by supporting cells called sustentacular cells. It is now clear that the loss of smell is related to the massive infection by SARS-CoV-2 of the sustentacular cells in the olfactory epithelium leading to its desquamation. However, the molecular mechanism behind the destabilization of the olfactory epithelium is less clear. Using golden Syrian hamsters infected with an early circulating SARS-CoV-2 strain harboring the D614G mutation in the spike protein; we show here that rather than being related to a first wave of apoptosis as proposed in previous studies, the innate immune cells play a major role in the destruction of the olfactory epithelium. We observed that while apoptosis remains at a low level in the damaged area of the infected epithelium, the latter is invaded by Iba1(+) cells, neutrophils and macrophages. By depleting the neutrophil population or blocking the activity of neutrophil elastase-like proteinases, we could reduce the damage induced by the SARS-CoV-2 infection. Surprisingly, the impairment of neutrophil activity led to a decrease in SARS-CoV-2 infection levels in the olfactory epithelium. Our results indicate a counterproductive role of neutrophils leading to the release of infected cells in the lumen of the nasal cavity and thereby enhanced spreading of the virus in the early phase of the SARS-CoV-2 infection.

Domaines

Immunologie

Dates et versions

hal-03918364 , version 1 (02-01-2023)

Identifiants

Citer

Clara Bourgon, Audrey St Albin, Ophélie Ando-Grard, Bruno da Costa, Roxane Domain, et al.. Neutrophils play a major role in the destruction of the olfactory epithelium during SARS-CoV-2 infection in hamsters. Cellular and Molecular Life Sciences, 2022, 79 (12), pp.616. ⟨10.1007/s00018-022-04643-1⟩. ⟨hal-03918364⟩
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