La mélanine de la paroi sporale d’Aspergillus module le métabolisme macrophagique

La mélanine de la paroi sporale d’Aspergillus module le métabolisme macrophagique

Nous souhaitons ce mois-ci mettre en avant un article très intéressant à la frontière de la biochimie, de la biologie cellulaire, de l’immunologie et de la microbiologie qui a été publié récemment dans Nature Communications. Cette publication du groupe de recherche de Cristina Cunha et Agostinho Carvalho (Institut de recherche en sciences de la vie et de la santé (ICVS), École de médecine, Université du Minho, Braga, Portugal) présente des avancées majeures concernant la capacité de la mélanine présente à la surface des spores d’Aspergillus à réguler le métabolisme des macrophages pulmonaires.

Le rôle de la reprogrammation métabolique des cellules immunitaires innées pour générer une inflammation protectrice et stimuler les défenses antimicrobiennes est largement documenté. Dans cet excellent article impliquant notamment notre collègue Jean-Paul Latgé, les auteurs ont établi que la mélanine fongique module l’induction de la glycolyse dans les macrophages ainsi que les réponses immunitaires antifongiques qui en résultent. La DHN-mélanine est un déterminant majeur de l’interaction fongique avec le système immunitaire inné, conférant aux moisissures environnementales (ici Aspergillus) la capacité de survivre à la destruction des phagocytes, notamment en bloquant la biogenèse des phagosomes et l’acidification des phagolysosomes, et en empêchant l’apoptose des phagocytes. Dans la présente publication, ils montrent que l’hôte a cependant développé des stratégies pour contrer les mécanismes inhibiteurs déployés par la mélanine. Ceci implique en particulier la détection de l’élimination de la mélanine lors du remodelage de la paroi cellulaire à l’intérieur du phagosome et l’utilisation de ces signaux pour réorienter le métabolisme cellulaire et promouvoir la réponse immunitaire antifongique.

En conclusion, ces résultats apportent de nouvelles connaissances mécanistiques sur l’interaction entre Aspergillus et le métabolisme du glucose dans les cellules immunitaires. Il est cependant probable que d’autres voies métaboliques interviennent également dans la régulation de cette immunité antifongique. Malheureusement, les technologies actuellement disponibles limitent encore l’obtention d’une vue d’ensemble des circuits cellulaires, des voies métaboliques et de leurs interconnexions qui sous-tendent ces processus immunitaires complexes. Quoi qu’il en soit, ce très bel article fournit des données sans précédent suggérant le rôle central de la glycolyse macrophagique et représente une première étape prometteuse vers une meilleure compréhension des caractéristiques métaboliques impliquées dans la régulation de l’immunité antifongique. Des approches immunomodulatrices ou des adjuvants métaboliques devraient donc être envisagés dans un proche avenir pour réorienter les cellules hôtes vers une protection immunitaire contre les infections fongiques. Ceci s’inscrit bien évidemment dans la tendance actuelle qui vise à développer des thérapies innovantes dirigées vers l’hôte.

Nicolas Papon, Christophe D’Enfert, Jean-Philippe Bouchara, Jean-Pierre Gangneux, Yves Delneste

Reference : Gonçalves, S.M., et al. (2020) Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity. Nat. Commun. 11, 2282.

Illustration tirée de PMID: 32622750
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