MAPK pathways regulated apoptosis and pyroptosis in respiratory epithelial cells of a primitive vertebrate model during bacterial infection

Abstract

Respiratory diseases caused by bacterial and viral infection have seriously affected human health. The invaginated lung structure in mammals caused difficulties in relevant research, here we evaluated the regulatory roles of MAPK pathways in apoptosis and pyroptosis during bacterial infection in an evaginated respiratory organ model for the first time. F. columnare was adopted for bacterial infection in rainbow trout in vivo and RTgill-W1 cells in vitro. Infected trout gills were separated for histological analysis, transcriptomic sequencing, TUNEL, RT-qPCR and enzyme activity assay. RTgill-W1 cells were treated with different inhibitors of MAPK pathway for evaluating apoptosis and pyroptosis. Bacterial infection induced serious histological changes and apoptosis in trout gill, accompanied with p38MAPK/ JNK pathway activation, while pyroptosis were induced after secondary infection along with ERK pathway activation. In vitro study confirmed pro-apoptotic roles of bacterial infection, accompanied with the increased phosphorylation of p38 MAPK and JNK. Moreover, p38 MAPK inhibition significantly decreased the F. columnare infection-induced apoptosis of RTgill-W1 cell via affecting Bcl2 protein expression and mitochondrial membrane potential. Therefore, our study indicated that MAPK pathways regulated apoptosis and pyroptosis in teleost respiratory organ during bacterial infection, which will benefit developing strategies in fighting against bacterial disease in aquaculture practice.

Keywords: Bacterial infection; MAPK pathways; Programmed cell death; Respiratory epithelial cells.