Long-Term Regulation of IL-17 Expression in Pacific Oyster Hemocytes by mGluR5 Through the Phosphoinositide Pathway

Metabotropic glutamate receptor 5 (mGluR5) is a critical regulator of immune responses within the neuroimmune system, influencing cytokine secretion and immune cell function. Although extensively studied in mammals, its role in regulating IL-17 in invertebrate immunity is poorly understood. This study examines <i>CgmGluR5</i> expression and downstream signaling activation in Pacific oyster (<i>Crassostrea gigas</i>) hemocytes following glutamate (Glu) and <i>Vibrio splendidus</i> treatment. Glu treatment significantly induced the expression of <i>CgmGluR5</i> and key signaling molecules, including PLC, DAG, IP3, Ca²⁺, and PKC, while enhancing mRNA levels of <i>CgIL17-1</i>, <i>CgIL17-5</i>, and <i>CgCaspase3</i>. Elevated Ca²⁺ content and <i>CgIL17</i> expression in hemocytes were observed at 12 h post-Glu exposure, indicating <i>CgmGluR5</i>-mediated immune regulation through the phosphoinositide pathway. A 1.14-fold increase in the apoptosis rate was found in the Glu treatment group compared to the control group. Knockdown of <i>CgmGluR5</i> suppressed <i>CgIL17-1</i> and <i>CgIL17-5</i> expression and reduced granulocyte proportions, reflecting its role in immune regulation. This study shows that <i>CgmGluR5</i> mediates long-term immune regulation in oysters through the phosphoinositide pathway, providing new theoretical insights for aquaculture immune management.