Effects of α and β-adrenergic signaling on innate immunity and Porphyromonas gingivalis virulence in an invertebrate model

To investigate the role of adrenergic signalling (AS) in the host immune response and <i>Porphyromonas gingivalis</i> virulence, we compared norepinephrine (NE) and isoproterenol (ISO) responses in <i>Galleria mellonella</i>. <i>P. gingivalis</i> infection was evaluated by survival; humoral immune responses (i.e. melanization and <i>cecropin</i> and <i>gloverin</i> mRNA expression); cellular immune responses (i.e. haemocyte count, nodulation by histology); and <i>P. gingivalis</i> recovery (CFU/mL). <i>P. gingivalis</i> was cultivated in the presence of ISO (PgISO) or NE and injected into the larvae for survival evaluation. Finally, we co-injected ISO and PgISO to evaluate the concomitant effects on the immune response and bacterial virulence. None of the ligands were toxic to the larvae; ISO increased haemocyte number, even after <i>P. gingivalis</i> infection, by mobilizing sessile haemocytes in a β-adrenergic-specific manner, while NE showed the opposite effect. ISO treatment reduced larval mortality and the number of recovered bacteria, while NE increased mortality and showed no effect on bacterial recovery. ISO and NE had similar effects on melanization and decreased the expression of cecropin. Although co-cultivation with NE and ISO increased the gene expression of bacterial virulence factors <i>in vitro</i>, only the injection of PgISO increased larval death, which was partially reversed by circulating ISO. Therefore, α- and β-adrenergic signalling had opposite effects after <i>P. gingivalis</i> infection. Ultimately, the catecholamine influence on the immune response overcame the effect of more virulent strains. The effect of AS directly on the pathogen found <i>in vitro</i> did not translate to the <i>in vivo</i> setting.