Cell Signaling of in Response to Enterotoxigenic Infection and Protection.

Enterotoxigenic (ETEC) infection causes the death of , which can be prevented by certain isolates. The host response of to ETEC infection and its regulation by the isolates are, however, largely unclear. This study has revealed that, in agreement with the results of life-span assays, the expression of the genes encoding p38 mitogen-activated protein kinase (MAPK) pathway (, and ), insulin/insulin-like growth factor (DAF/IGF) pathway (), or antimicrobial peptides (, and ) and other defensing molecules () was upregulated significantly when the wild-type nematode (N2) was subjected to ETEC infection. This upregulation was further enhanced by the pretreatment with LB1, but not with CL11. Mutants defective in the cell signaling of were either more susceptible (defective in NSY-1, SEK-1, PMK-1, or DAF16) or more resistant (defective in AGE-1, DBL-1, SKN-1, or SOD-3) to ETEC infection compared with the wild-type. Mutants defective in antimicrobial peptides (LYS-7, SPP1, or ABF-3) were also more susceptible. In addition, mutants that are defective in NSY-1, SEK-1, PMK-1, DAF16, ABF-3, LYS-7, or SPP1 showed no response to the protection from . LB1. The expression of the genes encoding antimicrobial peptides (, and ) and other defensing molecules (, and ) were almost all upregulated in AGE-1- or DBL-1-defective mutant compared with the wild-type, which was further enhanced by the pretreatment of LB1. The expression of these genes was, however, mostly downregulated in NSY-1- or DAF-16-defective mutant. These results suggest that LB1 regulates signaling through the p38 MAPK and DAF/IGF pathways to control the production of antimicrobial peptides and defensing molecules to combat ETEC infection.