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Article Dans Une Revue Gut Année : 2022

CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival

Camille Danne
Chloé Michaudel
Jurate Skerniskyte
  • Fonction : Auteur
Julien Planchais
  • Fonction : Auteur
Aurélie Magniez
Allison Agus
  • Fonction : Auteur
Marie-Laure Michel
Bruno Lamas
Gregory da Costa
  • Fonction : Auteur
Madeleine Spatz
  • Fonction : Auteur
Cyriane Oeuvray
  • Fonction : Auteur
Chloé Galbert
  • Fonction : Auteur
Maxime Poirier
  • Fonction : Auteur
Yazhou Wang
  • Fonction : Auteur
Alexia Lapière
  • Fonction : Auteur
Nathalie Rolhion
  • Fonction : Auteur
Tatiana Ledent
  • Fonction : Auteur
Cédric Pionneau
  • Fonction : Auteur
Solenne Chardonnet
  • Fonction : Auteur
Floriant Bellvert
Edern Cahoreau
Amandine Rocher
Rafael Rose Arguello
  • Fonction : Auteur
Carole Peyssonnaux
  • Fonction : Auteur
Sabine Louis
  • Fonction : Auteur
Mathias Richard
  • Fonction : Auteur
Philippe Langella
  • Fonction : Auteur
Jamel El-Benna
Benoit Marteyn
  • Fonction : Auteur
Harry Sokol

Résumé

Objectives Inflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 ( Card9 ), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown. Design We used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of Card9 deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real-time bioenergetic profile analysis (Seahorse). Results Lymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction increases mitochondrial reactive oxygen species production leading to the premature death of neutrophilsthrough apoptosis, especially in oxidative environment. The decreased functional neutrophils in tissues might explain the impaired containment of fungi and increased susceptibility to intestinal inflammation. Conclusion These results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils.

Domaines

Immunologie

Dates et versions

hal-03812185 , version 1 (12-10-2022)

Identifiants

Citer

Camille Danne, Chloé Michaudel, Jurate Skerniskyte, Julien Planchais, Aurélie Magniez, et al.. CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival. Gut, 2022, pp.gutjnl-2022-326917. ⟨10.1136/gutjnl-2022-326917⟩. ⟨hal-03812185⟩

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