Nous avons remarqué un article très intéressant à la frontière de la biologie cellulaire, de la microbiologie et de l’immunologie qui vient d’être publié le mois dernier dans Nature Communications. Cette publication du groupe de recherche de Christine Skerka (Département de biologie des infections, Institut Leibniz de recherche sur les produits naturels et de biologie des infections, Iéna, Allemagne) représente en effet une formidable avancée dans ces domaines.
Il avait été précédemment démontré que les vésicules extracellulaires (EV) sont des régulateurs centraux de la réponse immunitaire et sont utilisées comme une forme de communication cellulaire, en particulier lors d’infections bactériennes ou virales. Cependant, la génération, la composition et l’action des EV libérées par les cellules immunitaires lors d’infections fongiques in vivo n’étaient jusqu’alors pas décrites. Dans cette étude, Halder et ses collègues décrivent pour la première fois la mise en place d’une réponse immunitaire précoce à une infection fongique médiée par des EV monocytaires humains. Ils montrent que la levure opportuniste Candida albicans imite les cellules apoptotiques en induisant la libération d’EV à partir de monocytes sanguins humains qui transportent le TGF-β1 vers d’autres cellules. De ce fait, le TGF-β1 contribue de manière significative au développement d’une tolérance immunitaire sur les surfaces muqueuses promouvant le commensalisme de C. albicans. Cependant, lors d’une infection systémique, les EV transportant le TGF-β1 peuvent réduire la réponse immunitaire de l’hôte contre le champignon, ce qui favorise la survie des cellules fongiques. Ainsi, C. albicans peut réduire l’émission très précoce de cytokines pro-inflammatoires chez l’hôte en induisant la production de vésicule TGF-β1. Les auteurs émettent l’hypothèse que cette suppression précoce d’une réponse pro-inflammatoire se produit naturellement dans l’intestin en réponse au microbiome, mais que la suppression est préjudiciable à l’hôte dans une infection systémique.
Les limites thérapeutiques actuelles et les préoccupations concernant l’émergence des phénomènes de résistance aux antifongiques inspirent la recherche de nouvelles thérapies dirigées vers l’hôte. Cet article fournit ainsi de premières pistes dans l’optique d’innovations thérapeutiques pour les infections à levures du genre Candida, mais également met en lumière le potentiel du β-glucane soluble (issu de la paroi de ces levures) en tant qu’immunosuppresseur dans le cadre des maladies inflammatoires.
Référence :
Halder, L.D. et al. (2020) Immune modulation by complement receptor 3-dependent human monocyte TGF-β1-transporting vesicles. Nat. Commun. 11, 233
La section Mycologie
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