AUTHOR=Zhou Mengzhou , Liu Xiaozhen , Yu Hai , Yin Xianhua , Nie Shao-Ping , Xie Ming-Yong , Chen Wei , Gong Joshua 

TITLE=Cell Signaling of Caenorhabditis elegans in Response to Enterotoxigenic Escherichia coli Infection and Lactobacillus zeae Protection

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01745

DOI=10.3389/fimmu.2018.01745

ISSN=1664-3224

ABSTRACT=<p>Enterotoxigenic <italic>Escherichia coli</italic> (ETEC) infection causes the death of <italic>Caenorhabditis elegans</italic>, which can be prevented by certain <italic>Lactobacillus</italic> isolates. The host response of <italic>C. elegans</italic> 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 (<italic>nsy-1, sek-1</italic>, and <italic>pmk-1</italic>), insulin/insulin-like growth factor (DAF/IGF) pathway (<italic>daf-16</italic>), or antimicrobial peptides (<italic>lys-7, spp-1</italic>, and <italic>abf-3</italic>) and other defensing molecules (<italic>abf-2, clec-85</italic>) was upregulated significantly when the wild-type nematode (N2) was subjected to ETEC infection. This upregulation was further enhanced by the pretreatment with <italic>Lactobacillus zeae</italic> LB1, but not with <italic>L. casei</italic> CL11. Mutants defective in the cell signaling of <italic>C. elegans</italic> 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 <italic>L</italic>. <italic>zeae</italic> LB1. The expression of the genes encoding antimicrobial peptides (<italic>lys-7, spp-1</italic>, and <italic>abf-3</italic>) and other defensing molecules (<italic>abf-2, clec-60</italic>, and <italic>clec-85</italic>) 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 <italic>L. zeae</italic> LB1. The expression of these genes was, however, mostly downregulated in NSY-1- or DAF-16-defective mutant. These results suggest that <italic>L. zeae</italic> LB1 regulates <italic>C. elegans</italic> signaling through the p38 MAPK and DAF/IGF pathways to control the production of antimicrobial peptides and defensing molecules to combat ETEC infection.</p>