Dahai Yang

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 BGpretreatment 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 BGpretreatment, 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.

B lymphocytes engaged in humoral immunity play a critical role in combating pathogenic infections; however, the mechanisms of NK cells in regulating the responses of B cells remain largely unknown. In the present study, we established an Edwardsiella piscicida infection model in turbot (Scophthalmus maximus) and found that the production of IgM was decreased. Meanwhile, through establishing the head kidney-derived lymphocyte infection model, we revealed that the impairment of IgMhi B cells was associated with bacterial infection–induced perforin production. Interestingly, we reveal that perforin production in NK cells is tightly regulated by an inhibitory novel immune-type receptor, NITR12. Moreover, we confirm that inhibiting NITR12 can result in elevated perforin production, engaging the impairment of IgMhi B cells. Taken together, these findings demonstrate an innovative strategy of NK cells in mediating B lymphocyte killing in turbot and suggest that relieving NK cells through NITR12 might be the target for the development of efficacious vaccines.