Negative regulation of suppressor of cytokine signaling 3a and 3b for antibacterial immunity in Cyprinus carpio infected by Aeromonas hydrophila.

Suppressor of Cytokine Signaling 3 (SOCS3) plays a crucial negative regulatory role in maintaining immune homeostasis, but its function in the antibacterial immunity of common carp Cyprinus carpio remains unclear. In this study, Ccsocs3a and Ccsocs3b were cloned and identified in C. carpio for the first time. Their sequence characteristics, evolutionary relationships, and tissue expression profiles were systematically analyzed. The results showed that CcSOCS3a and CcSOCS3b contain typical conserved domains of SOCS proteins and exhibit high expression levels in immune-related tissues, including the head kidney, spleen, and gill. Infection with Aeromonas hydrophila significantly upregulated the transcriptional and protein levels of CcSOCS3a and CcSOCS3b in various tissues. CcSOCS3a and CcSOCS3b inhibited the JAK2/STAT3 pathway and the production of proinflammatory cytokines (IL-6 and TNF-α), as shown by functional assays. Further investigation demonstrated that overexpression of CcSOCS3a or CcSOCS3b significantly increased bacterial load in tissues and reduced survival rates. In summary, this study reveals the immunosuppressive roles of CcSOCS3a and CcSOCS3b during A. hydrophila infection, providing new insights into the structure and function of SOCS3 proteins in teleost, as well as identifying potential molecular targets for immune regulation against bacterial diseases in aquaculture.