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In the present study, CgC3 in the cell-free hemolymph of the Pacific oyster Crassostrea gigas was found to be able to bind various polysaccharides and microbes and then interacted with membrane receptor CgCD18 to mediate the entry of the CgC3-coated Vibrio into hemocytes. CgATPV1D in hemocytes sensed the CgC3-coated Vibrio vacuole and recruited CgATG16L1. The free CgC3 in hemocytes could also recognize and bind the intracellular invading Vibrio and then directly recruited CgATG16L1. CgATG16L1 recruited CgLC3 to promote the extension of autophagosome membrane. The autophagosome then fused with lysosome to form autolysosome to degrade the CgC3-coated Vibrio. When the C3-CD18-ATG16L1 axis was destroyed by their antibodies, dsRNAs or siRNAs, the co-localizations of Vibrio, CgC3, CgATPV1D, CgATG16L1, CgLC3, and lysosome were all inhibited in hemocytes. The cleavage of CgLC3 and the amount of autophagosomes and autolysosomes were also reduced after Vibrio stimulation. The results collectively demonstrated that CgC3 was able to bind intra\/extracellular microbes to form intracellular microbe\u2013associated complexes of C3-CD18-ATPV1D-ATG16L1-LC3 and C3-ATG16L1-LC3, and then trigger the intracellular antibacterial autophagy-lysosome pathway to eliminate the invading microbes.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf290","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T16:36:38Z","timestamp":1764434198000},"source":"Crossref","is-referenced-by-count":0,"title":["C3-CD18-VATPase-ATG16L1 and C3-ATG16L1 axes restrict the escape of microbes through the autophagy-lysosome pathway"],"prefix":"10.1093","volume":"215","author":[{"given":"Wenwen","family":"Yang","sequence":"first","affiliation":[{"name":"Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University , Dalian,","place":["China"]},{"name":"Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University , 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