Trained immunity amplifies intestinal complement 3 to maintain Th17 cells against bacterial infection-induced enteritis in zebrafish

Infectious enteritis is often accompanied with immuno-disorder of intestinal immune cells caused by microbials infection. Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. However, whether the induction of trained immunity plays a role in protecting infectious enteritis remains largely unknown. Here, through establishing an in vivo ß-glucan training and E. piscicida infection model in zebrafish, we observe that induction of trained immunity could alleviate bacterial infection-caused enteritis. Moreover, we identify intestinal complement C3 as a crucial target of trained immunity and could be amplified in response to bacterial infection. Furthermore, we reveal that trained immunity could reverse the reduction of intestinal Th17 cells in C3-dependent manner to alleviate infectious enteritis. Taken together, our results uncover the role of complement C3-mediated trained immunity in maintaining Th17 cells and intestine homeostasis, and provide a theoretical strategy for immunotherapies of infectious enteritis. Overall design: RNA-seq profiling of wildtype zebrafish in mock and PBS- or ß-glucan-trained at Day 7 after secondary E. piscicida infection