Mieux comprendre l’interaction de Candida auris avec notre système immunitaire

Mieux comprendre l’interaction de Candida auris avec notre système immunitaire

La levure Candida auris fait couler beaucoup d’encre depuis ces dernières années. Elle est parmi les agents pathogènes fongiques émergents les plus préoccupants puisque le plus souvent résistante à la plupart des antifongiques actuellement disponibles pour le traitement des infections invasives. Nous souhaitons mettre en avant ce mois-ci un excellent article paru récemment dans la revue Nature Microbiology et qui montre pour la première fois comment cette levure opportuniste interagit avec notre système immunitaire. Grace à de multiples approches, le groupe de recherche mené par Mihai G Netea (Division of Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands) montre en effet que cette levure induit une réponse immunitaire bien plus prononcée que celle observée pour Candida albicans (responsable de la majorité des candidoses mortelles). Plus précisément, l’activation immunitaire innée induite par la levure est médiée par la reconnaissance de mannoprotéines structurellement uniques à C. auris. Ces résultats démontrent ainsi pour la première fois que C. auris est un puissant inducteur des mécanismes de défense innée de l’hôte et identifient par ce biais des cibles possibles pour de futurs développements thérapeutiques visant à mieux traiter ces infections fongiques.

Nicolas Papon, Marie-Noëlle Rosso, Christophe D’Enfert, Jean-Philippe Bouchara

Reference : Bruno et al., Nat Microbiol. 2020 Dec;5(12):1516-1531.

Évolution possible des interactions phagocyte – C. auris et rôle clé des mannoprotéines fongiques. (A) Interactions avec les cellules phagocytaires. Après la reconnaissance, les levures bourgeonnantes sont internalisées dans une grande vésicule intracytoplasmique appelée phagosome. Rapidement, soit la levure est lysée, grâce à la fusion des lysosomes (vésicules blanches et petites) avec le phagosome, soit échappe à la lyse. Les cellules de Candida auris disséminent alors par voie sanguine pour provoquer une infection profonde potentiellement mortelle. (B) Aspects moléculaires de ces interactions. La surface cellulaire de la levure présente des mannoprotéines avec des chaînes latérales spécifiques d’α-1,2-mannose-phosphate (M-α-1-phosphate). Bruno et ses collègues montrent dans cet article le rôle important des récepteurs macrophagiques pour le mannose (MMR) ou la forme inactive du composant C3 du complément, le C3bi (CR3), dans la reconnaissance de ces mannoprotéines spécifiques et dans l’induction ultérieure d’une réponse immunitaire marquée. Illustration adaptée de Chaturvedi et al., 2020.
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