SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance

Rémy Robinot (1) , Mathieu Hubert (1) , Guilherme Dias de Melo (2) , Françoise Lazarini (3) , Timothée Bruel (1) , Nikaïa Smith (4) , Sylvain Levallois (5) , Florence Larrous (2) , Julien Fernandes (6) , Stacy Gellenoncourt (1) , Stéphane Rigaud (7) , Olivier Gorgette (8) , Catherine Thouvenot (8) , Céline Trébeau (9) , Adeline Mallet (8) , Guillaume Duménil (8) , Samy Gobaa (10) , Raphael Etournay (9) , Pierre-Marie Lledo (3) , Marc Lecuit (5) , Hervé Bourhy (2) , Darragh Duffy (4) , Vincent Michel (9, 11) , Olivier Schwartz (1, 12) , Lisa Chakrabarti (1)

1 CNRS-UMR3569 - Virus et Immunité - Virus and immunity
2 Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology
3 Perception et Mémoire / Perception and Memory
4 Immunologie Translationnelle - Translational Immunology lab
5 Biologie des Infections - Biology of Infection
6 UTechS PBI - BioImagerie Photonique – Photonic BioImaging
7 IAH - Hub d'analyse d'images - Image Analysis Hub (Platform)
8 UTechS UBI - Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform
9 IDA - Institut de l'Audition [Paris]
10 Plateforme technologique Biomatériaux et Microfluidique - Biomaterials and Microfluidics technologic Platform
11 INSERM - Institut National de la Santé et de la Recherche Médicale
12 VRI - Vaccine Research Institute [Créteil, France]

Understanding how SARS-CoV-2 spreads within the respiratory tract is important to define the parameters controlling the severity of COVID-19. We examined the functional and structural consequences of SARS-CoV-2 infection in a reconstituted human bronchial epithelium model. SARS-CoV-2 replication caused a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remained limited. Rather, SARS-CoV-2 replication led to a rapid loss of the ciliary layer, characterized at the ultrastructural level by axoneme loss and misorientation of remaining basal bodies. The motile cilia function was compromised, as measured in a mucociliary clearance assay. Epithelial defense mechanisms, including basal cell mobilization and interferon-lambda induction, ramped up only after the initiation of cilia damage. Analysis of SARS-CoV-2 infection in Syrian hamsters further demonstrated the loss of motile cilia in vivo . This study identifies cilia damage as a pathogenic mechanism that could facilitate SARS-CoV-2 spread to the deeper lung parenchyma.

Domaines: Immunologie

Rémy Robinot, Mathieu Hubert, Guilherme Dias de Melo, Françoise Lazarini, Timothée Bruel, et al.. SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance. 2021. ⟨pasteur-03244406⟩