The intracellular bacteria-triggered CBM complex regulates the expressions of inflammatory cytokines in oyster

The CARD-BCL10-MALT1 (CBM) complex is a key substance in the immune system that regulates innate and adaptive immune responses. It is assembled by three core proteins (CARD containing coiled-coil protein, BCL10, and MALT1) through specific interactions. This study focused on the CARD14-BCL10-MALT1 complex of oyster Crassostrea gigas, and systematically studied its identification, activation mechanism, and regulation for inflammation and immunity. CARD14, BCL10 and MALT1 homologs (defined as CgCARD14, CgBCL10 and CgMALT1, respectively) were identified from C. gigas, and they were highly expressed in hemocytes and gills. After Vibrio splendidus stimulation, the mRNA expressions of CgCARD14, CgBCL10 and CgMALT1 increased significantly in hemocytes. CgCARD14, CgBCL10 and CgMALT1 all could bind and co-localize with bacteria through their specific domains. Upon binding bacteria, CgCARD14, CgBCL10 and CgMALT1 could interact to form large CARD14-BCL10-MALT1 complex containing bacteria, which then promoted the nuclear translocation of CgAP-1 and regulated the mRNA expressions of CgTNF-1, CgHMGB1, and CgDefh. The results suggested that upon sensing bacteria, the large CARD14-BCL10-MALT1 complex was activated to promote CgAP-1 nuclear translocation, ultimately regulating the expression of immune effectors in oyster. Thus, a novel activation mechanism of CBM complex independent of the activating receptor was proposed in oyster.