Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage

Joy Lachat, Alice Pascault, Delphine Thibaut, Rémi Borgne, Jean-Marc Verbavatz and Allon Weiner ()
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Joy Lachat: Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses, Cimi-Paris
Alice Pascault: Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses, Cimi-Paris
Delphine Thibaut: Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses, Cimi-Paris
Rémi Borgne: Université Paris Cité, CNRS, Institut Jacques Monod
Jean-Marc Verbavatz: Université Paris Cité, CNRS, Institut Jacques Monod
Allon Weiner: Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses, Cimi-Paris

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract The opportunistic fungal pathogen Candida albicans is normally commensal, residing in the mucosa of most healthy individuals. In susceptible hosts, its filamentous hyphal form can invade epithelial layers leading to superficial or severe systemic infection. Although invasion is mainly intracellular, it causes no apparent damage to host cells at early stages of infection. Here, we investigate C. albicans invasion in vitro using live-cell imaging and the damage-sensitive reporter galectin-3. Quantitative single cell analysis shows that invasion can result in host membrane breaching at different stages and host cell death, or in traversal of host cells without membrane breaching. Membrane labelling and three-dimensional ‘volume’ electron microscopy reveal that hyphae can traverse several host cells within trans-cellular tunnels that are progressively remodelled and may undergo ‘inflations’ linked to host glycogen stores. Thus, C. albicans early invasion of epithelial tissues can lead to either host membrane breaching or trans-cellular tunnelling.

Date: 2022
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DOI: 10.1038/s41467-022-31237-z

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