IgIT-Mediated Signaling Inhibits the Antimicrobial Immune Response in Oyster Hemocytes

The long-term evolutionary interaction between the host and symbiotic microbes determines their cooperative relationship. It is well known that the symbiotic microbes have evolved various mechanisms to either benefit or exploit the mammalian host immune system to maintain homeostasis. However, the strategies employed by the symbiotic microbes to overcome host immune responses in invertebrates are still not clear. In the current study, the hemolymph microbes in oyster Crassostrea gigas were found to be able to directly bind an oyster Ig superfamily member (IgSF) (designated as CgIgIT) to inhibit the immune responses of hemocytes. The mRNA transcripts of CgIgIT in hemocytes increased significantly after the stimulation with hemolymph microbes. CgIgIT was found to be located on the hemocyte membrane and it was able to directly bind the hemolymph microbes and polysaccharides via its three Ig domains and recruited the protein tyrosine phosphatase CgSHP2 through its ITIM. The recruited CgSHP2 inhibited the activities of CgERK, CgP38 and CgJNK proteins to reduce the productions of dual oxidase 2 (CgDuox2) and defensin 2 (CgDef2), which eventually protected the hemolymph microbes from CgDuox2/CgDef2-mediated elimination. Collectively, the results suggest that the oyster IgIT-SHP2 signaling pathway can recognize bacteria capable of residing in oyster hemolymph and inhibit innate immune responses, which contributes to the maintenance, colonization, and survival of hemolymph microbes.