Hemocyanin controls <i>Vibrio</i> levels in hemolymph by modulating intracellular ROS via p38 MAPK

Redox reactions are essential for various biological processes, hence, maintaining redox homeostasis is critical for cellular health and host-microbe interactions, particularly in marine invertebrates, where these processes remain poorly understood. This study investigates the role of the respiratory protein hemocyanin in regulating redox-related genes, reactive oxygen species (ROS) levels in shrimp hemocytes, and its influence on immune function and hemolymph <i>Vibrio</i> abundance. Our results show that hemocyanin is crucial in the regulation of the redox system, as hemocyanin knockdown disrupts the expression of antioxidant (<i>Pv</i>POD and <i>Pv</i>GPX) and pro-oxidant (<i>Pv</i>XOX) genes and redox enzyme activities, leading to elevated ROS levels in hemocytes. Additionally, we found that hemocyanin controls redox homeostasis in hemocytes through the p38-MAPK-c-Jun signaling pathway. Moreover, ROS levels regulated by hemocyanin via the MAPK pathway impacted on hemolymph <i>Vibrio</i> spp. abundance. These findings highlight a crucial role of hemocyanin as an antioxidant that modulates redox balance in shrimp hemocytes, with significant implications for immune defense and microbial homeostasis, offering new insights into antioxidative mechanisms in marine invertebrates.