| Abstract |
Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a pattern recognition receptor of bacterial peptidoglycans. NOD1 facilitates the elimination of invading intracellular bacteria via autophagy induction. Here, we demonstrate that NOD1 exerts an anti-inflammatory effect mediated via the selective autophagy of host cell protein. In our study of Candida albicans water-soluble fraction (CAWS)-induced coronary arteritis, which is a mouse model of Kawasaki disease, we observed an exacerbated disease phenotype in NOD1-deficient mice. NOD1 deficiency induced a higher expression of inflammatory cytokines via CAWS and CAWS-induced endoplasmic reticulum (ER) stress in bone marrow-derived dendritic cells. Furthermore, exaggerated inflammation was dependent on apoptosis signal-regulated kinase 1 (ASK1). Notably, NOD1 directly interacted with ASK1, inducing selective autophagy of ASK1, which was dependent on ATG16L1, and thus competitively inhibiting ER stress-dependent ASK1 activation. Altogether, these results show that NOD1 modulates excessive inflammatory responses through the upregulation of autophagy.
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