NOD1 sensing of house dust mite-derived microbiota promotes allergic experimental asthma

Saliha Ait Yahia (1) , Camille Audousset (1) , Daniel Alvarez-Simon (1) , Han Vorng (1) , Dieudonnée Togbe (2) , Philippe Marquillies (1) , Myriam Delacre (1) , Stéphanie Rose (2) , Hélène Bouscayrol (2) , Aline Rifflet (3, 4) , Valérie Quesniaux (2) , Ivo Gomperts Boneca (3, 4) , Mathias Chamaillard (1) , Anne Tsicopoulos (1)

1 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
2 INEM - Immunologie et Neurogénétique Expérimentales et Moléculaires
3 Biologie Évolutive de la Cellule Microbienne - Evolutionary Biology of the Microbial Cell
4 INSERM - Institut National de la Santé et de la Recherche Médicale

Background Asthma severity has been linked to exposure to gram-negative bacteria from the environment that are recognized by NOD1 receptor and are present in house dust mite (HDM) extracts. NOD1 polymorphism has been associated with asthma. Objective We sought to evaluate whether either host or HDM-derived microbiota may contribute to NOD1-dependent disease severity. Methods A model of HDM-induced experimental asthma was used and the effect of NOD1 deficiency was evaluated. Contribution of host microbiota was evaluated by fecal transplantation. Contribution of HDM-derived microbiota was assessed by 16S ribosomal RNA sequencing, mass spectrometry analysis, and peptidoglycan depletion of the extracts. Results In this model, loss of the bacterial sensor NOD1 and its adaptor RIPK2 improved asthma features. Such inhibitory effect was not related to dysbiosis caused by NOD1 deficiency, as shown by fecal transplantation of Nod1-deficient microbiota to wild-type germ-free mice. The 16S ribosomal RNA gene sequencing and mass spectrometry analysis of HDM allergen, revealed the presence of some muropeptides from gram-negative bacteria that belong to the Bartonellaceae family. While such HDM-associated muropeptides were found to activate NOD1 signaling in epithelial cells, peptidoglycan-depleted HDM had a decreased ability to instigate asthma in vivo. Conclusions These data show that NOD1-dependent sensing of HDM-associated gram-negative bacteria aggravates the severity of experimental asthma, suggesting that inhibiting the NOD1 signaling pathway may be a therapeutic approach to treating asthma.

Mots clés: Asthma; allergy; house dust mite; Th2 cells; NOD1; peptidoglycan; epithelial cells; microbiota

Domaines: Sciences du Vivant [q-bio]

Saliha Ait Yahia, Camille Audousset, Daniel Alvarez-Simon, Han Vorng, Dieudonnée Togbe, et al.. NOD1 sensing of house dust mite-derived microbiota promotes allergic experimental asthma. Journal of Allergy and Clinical Immunology, 2021, 148 (2), pp.394-406. ⟨10.1016/j.jaci.2020.12.649⟩. ⟨hal-03429617⟩