IFN-γ Manipulates NOD1-Mediated Interaction of Autophagy and to Augment Intracellular Clearance in Fish.

is an intracellular pathogenic bacterium accounting for significant losses in farmed fish. Currently, cellular and molecular mechanisms underlying -host cross-talk remain obscure. In this study, we revealed that could increase microtubule-associated protein L chain 3 (LC3) puncta in grass carp () monocytes/macrophages and a carp cell line, The autophagic response was confirmed by detecting the colocalization of with LC3-positive autophagosomes and LysoTracker-probed lysosomes in the cells. Moreover, we unveiled the autophagic machinery targeting by which the nucleotide-binding oligomerization domain receptor 1 (NOD1) functioned as an intracellular sensor to interact and recruit autophagy-related gene (ATG) 16L1 to the bacteria. Meanwhile, decreased the mRNA and protein levels of NOD1 and ATG16L1 in an estrogen-related receptor-α-dependent manner, suggesting a possible mechanism for this bacterium escaping autophagy. Subsequently, we examined the effects of various virulence factors on NOD1 expression and found that two of them, EVPC and ESCB, could reduce NOD1 protein expression via ubiquitin-dependent proteasomal degradation. Furthermore, an intrinsic regulator IFN-γ was found to enhance the colocalization of with NOD1 or autophagosomes, suggesting its involvement in the interaction between autophagy and Along this line, a short-time treatment of IFN-γ caused intracellular clearance through an autophagy-dependent mechanism. Collectively, our works demonstrated NOD1-mediated autophagy- dialogues and uncovered the molecular mechanism involving autophagy against intracellular bacteria in fish.