Phagocytes activation by pathogens or stressors induces a shift toward aerobic glycolysis and glutamine-driven mitochondrial metabolism, supporting the energetic and biosynthetic demands of immune activation. Besides all the investigation on the metabolic and immune responses on mammals, in salmon phagocytic cells during P. salmonis infection has not been fully elucidated.
Using SHK-1 cell line, we established a model to investigate the effect of differential glutamine availability (0mM (IPM), 2mM (PM), 6mM (SPM) media) on response to infection with P. salmonis . We performed an in vitro infection assay o ver 10 days, we characterized the infection based on the cytopathic effect (CE) exhibited by the infected cells. T he results show that infected cells supplemented with glutamine (6 mM) showed a significant decrease in PCVs (Figure 1a) compared to cells infected in PM medium. Cell viability analysis revealed differential patterns depending on the availability of glutamine during infection. In SPM medium, infected cells showed a 22% reduction in viability compared to uninfected controls (Figure 5c). Contrary to intuition, in IPM (absence of exogenous glutamine), a lower impact on cell viability was observed (40% vs. controls), despite presenting a reduced cytopathic effect. This phenomenon contrasts sharply with the results in PM, where cell viability decreased by 50% in infected cells, highlighting a bimodal phenomenon dependent on the concentration of this amino acid. This phenomenon is consistent with previous studies demonstrating that glutamine enhances antioxidant capacity and the expression of proinflammatory cytokines in fish immune cells (Jiao et al., 2022), as well as its role in activating the OXPHOS pathways necessary for the elimination of intracellular pathogens (Ewald et al., 2024; Lebeau et al., 2024). However, the parallel reduction in cell viability (22% in SPM vs. 40% in IPM) indicates a critical balance between antimicrobial efficacy and energy cost to the host, a metabolic dilemma also observed in viral infections where gln availability differentially regulates antiviral genes dependent on glycolysis or OXPHOS (Lebeau et al., 2024).