Histamine-mediated immune regulation in pearl oysters (Pinctada fucata martensii): Insights into regulatory functions and mechanisms

Histamine (HA) serves as a crucial neurotransmitter in both vertebrates and invertebrates, exerting a pivotal role in immune regulation. However, the regulatory functions of HA in mollusks remain largely unexplored. In this study, we elucidate the regulatory functions of HA in immune responses elicited by lipopolysaccharide (LPS) and transplantation in pearl oysters ( Pinctada fucata martensii ). Our results showed that injection of HA prior to LPS stimulation significantly reduced the interleukin-17 (IL-17) content and antibacterial activity of serum. Concurrently, signal pathways such as the NOD-like receptor signaling pathway were inhibited, alongside a decrease in the expression level of CaM genes. Injection of HA prior to transplantation led to increased activity of superoxide dismutase and catalase in serum, coupled with a decrease in serum antibacterial activity. Additionally, signal pathways associated with apoptosis were suppressed, alongside a decrease in the expression level of CaM genes. Moreover, HA incubation post-transplantation at 3 and 6 h inhibited the concentration of Ca 2+ in hemocytes. TUNEL assay results indicated that HA inhibited hemocyte apoptosis induced by transplantation, suggesting a potential role of HA in suppressing humoral immunity and apoptosis while enhancing antioxidant capacity via calcium signaling. These findings offer novel insights into the immune regulatory mechanisms of HA in mollusks. • HA inhibits the inflammatory responses and humoral immunity induced by LPS. • HA attenuates oxidative stress by enhancing the antioxidant capacity of the transplanted pearl oysters. • HA modulates intracellular Ca 2+ by regulating IP3R upon HR activation. • HA inhibits the expression of PRR genes, immune recognition responses, and apoptosis.