β-Glucan-pretreatment amplifies lectin pathway to maintain the function of intestinal Th17 cells against infectious enteritis

Enteritis is often accompanied by immune cell dysfunction during intestinal infections. The β-glucans with immunomodulatory activities have been recently shown to support anti-bacterial immune responses through the induction of trained immunity. However, the potential role of β-glucan (BG)-pretreatment in protecting infectious enteritis in teleost fish remains largely unknown. Herein, through establishing a BG-pretreatment and Edwardsiella piscicida infection model in adult zebrafish, we demonstrated that BG-pretreatment confers protection against infectious enteritis, accompanying by reduced production of pro-inflammatory cytokines. Specifically, we found that BG-pretreatment could amplify the intestinal lectin pathway-engaged complement activation to mitigate the infectious enteritis. Moreover, through comprehensive analysis of immune cell’s marker genes in zebrafish RNA-seq data, we revealed that BG-pretreatment could modulate the responsiveness of intestinal Th17 cells through lectin pathway amplification, and this BG-pretreatment-mediated functional maintenance of Th17 cells is essential for protecting infectious enteritis. Collectively, these findings identify the intestinal lectin pathway as a potential effector of BG-pretreatment, and reveal its role in maintaining the function of Th17 cells in zebrafish, suggesting that harnessing the BG-engaged trained immunity might represent a promising therapeutic strategy against infectious enteritis in teleost.