β-Glucan pretreatment activates lectin pathway to maintain the function of intestinal Th17 cells for infectious...

Enteritis, involving inflammation of the small intestine, is often accompanied by immune cell dysfunction during intestinal infections. Immunomodulatory β-glucans (BGs) have recently been shown to support antibacterial immune responses through the induction of trained immunity. However, little is known about the potential role of BG pretreatment in protecting against infectious enteritis in teleost fish. In this work, by establishing an adult zebrafish enteritis model via infection with the fish pathogen Edwardsiella piscicida and pretreating it with BGs, we demonstrated that such pretreatment confers protection against infectious enteritis, accompanied by reduced production of proinflammatory cytokines. Specifically, we found that BG pretreatment could amplify intestinal lectin pathway-associated complement activation to ameliorate the infectious enteritis. Moreover, through comprehensive RNA-seq analysis of immune cell marker genes in zebrafish, we revealed that the lectin pathway amplification by BG pretreatment modulated the responsiveness of intestinal Th17 cells, which was essential for the protection against infectious enteritis. Collectively, these findings identify the intestinal lectin pathway as a potential mediator of the effects of BG pretreatment and reveal its role in maintaining the function of Th17 cells in zebrafish. This suggests that harnessing BG-induced trained immunity might represent a promising therapeutic strategy against infectious enteritis in teleost.