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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:148

Article

Yahia, Saliha Ait¹  Audousset, Camille¹  Alvarez-Simon, Daniel¹  Vorng, Han¹  Togbe, Dieudonnee²  Marquillies, Philippe¹  Delacre, Myriam¹  Rose, Stephanie²  Bouscayrol, Helene²  Rifflet, Aline^3,4,5  Quesniaux, Valerie²  Boneca, Ivo Gomperts^3,4,5  Chamaillard, Mathias¹  Tsicopoulos, Anne¹ 

[1] Univ Lille, Ctr Natl Rech Sci CNRS, Inst Natl Sante & Rech Med, Ctr Hosp Univ Lille,Inst Pasteur Lille,U1019 Unit, Lille, France

[2] UMR 7355 CNRS Univ Orleans, Lab Expt & Mol Immunol & Neurogenet, Orleans, France

[3] Inst Pasteur, Unite Biol & Genet Paroi Bacterienne, Paris, France

[4] CNRS, UMR 2001, Paris, France

[5] Inst Natl Sante & Rech Med, Equipe Avenir, Paris, France

关键词: Asthma;    allergy;    house dust mite;    NOD1;    peptidoglycan;    epithelial cells;    microbiota;    T(H)2 cells;   

DOI  :  10.1016/j.jaci.2020.12.649

来源: Elsevier

【 摘 要 】

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 HDMderived 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. (J Allergy Clin Immunol 2021;148:394-406.)

【 授权许可】

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