Implication of NOD-1 receptor in house dust mite (HDM)-induced asthma

Abstract

NOD1 is an innate pattern-recognition sensor for Gram-negative peptidoglycan (PG) that is involved in the development of allergic asthma and signals through the kinase RIPK2. The aim of this study was to investigate the role of NOD1 in HDM-induced asthma. Nod1 -/- , Ripk2 -/− and WT mice were subjected to a protocol of HDM-induced asthma. Faecal microbiota transplantation from Nod1 -/− and WT was performed in germ free (GF) mice before HDM asthma protocol. HDM content was analysed by mass spectrometry. A NOD1 reporter cell model and the human bronchial epithelial cell line Beas2B were stimulated with HDM. Nod1 -/− and Ripk2 -/− mice exhibited reduced asthma features, including decreased airway hyperresponsiveness (AHR), less pulmonary inflammation and lower levels of Th2-related cytokines and chemokines. However, no differences in any asthma parameters were found between GF mice transplanted with either Nod1 -/− or WT microbiota. HDM mass spectrometry analysis evidenced the presence of PG-derived NOD1 ligands, and a PG-dependent activation was found in the NOD1 reporter model. Furthermore, the HDM stimulation of human epithelial Beas2B cells led to NOD1 activation and RIPK2 signalling. Accordingly, when WT mice were subjected to the asthma protocol with PG-depleted HDM, but not to LPS-reduced HDM, asthma features were notably reduced. HDM-derived microbiota promotes allergic airway disease through NOD1 sensing, suggesting that this pathway may provide attractive therapeutic targets.