AUTHOR=Zhou Mengzhou , Liu Xiaozhen , Yu Hai , Gong Joshua 

TITLE=Lactobacillus Regulates Caenorhabditis elegans Cell Signaling to Combat Salmonella Infection

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.653205

DOI=10.3389/fimmu.2021.653205

ISSN=1664-3224

ABSTRACT=<p><italic>Salmonella typhimurium</italic> DT104 infection causes the death of <italic>Caenorhabditis elegans</italic>, which can be prevented by certain <italic>Lactobacillus</italic> isolates. However, the molecular mechanisms of both the host response to the infection and the protection by <italic>Lactobacillus</italic> are largely unclear. The present study has investigated the life-span and gene expression of both wild-type (WT) and mutants in some key components of cell signaling in response to <italic>S. typhimurium</italic> infection and protection from <italic>Lactobacillus zeae</italic>. The results indicated that the gene expression of <italic>daf-16</italic> in the DAF/ insulin-like growth factor (DAF/IGF) pathway, <italic>ced-3</italic> and <italic>ced-9</italic> in the programmed cell death (PCD) pathway, <italic>lys-7, spp-1</italic>, and <italic>abf-3</italic> for antimicrobial peptide production, and <italic>bar-1</italic> involved in the production of other defense molecules was all significantly upregulated when the wild-type (WT) was subjected to DT104 infection. On the contrary, the gene expression of <italic>tir-1, sek-1</italic>, and <italic>pmk-1</italic> in the p38 mitogen-activated protein kinase (MAPK) pathway and <italic>clec-60, sod-3</italic>, and <italic>skn-1</italic> for the production of other defense molecules was significantly suppressed by DT104. Pretreatment of the worms with <italic>L. zeae</italic> LB1 significantly upregulated the expression of almost all the tested genes except for <italic>ced-3, ced-9, abf-2, age-1</italic>, and <italic>dbl-1</italic> compared with the nematode infected with DT104 only. Mutants defective in the cell signaling or other defense molecules of <italic>C. elegans</italic> were either more susceptible (defective in <italic>nsy-1, sek-1, pmk-1, ced-3, ced-9, skn-1</italic>, or <italic>daf-16</italic>) or more resistant (defective in <italic>age-1</italic> or <italic>dbl-1</italic>) to DT104 infection than the WT except for the mutant defective in <italic>sod-3</italic>. Mutants defective in antimicrobial peptides (<italic>lys-7</italic> or <italic>abf-3</italic>) were also more susceptible than the WT. In contrast, the mutant defective in <italic>spp-1</italic> became more resistant. When all the mutants were pretreated with <italic>L. zeae</italic> LB1, five mutants that are defective in <italic>nsy-1, sek-1, pmk-1, abf-3</italic>, or <italic>lys-7</italic> showed no response to the protection from LB1. These results suggest that <italic>L. zeae</italic> LB1 can regulate <italic>C. elegans</italic> cell signaling including the p38 MAPK pathway and downstream production of antimicrobial peptides and defense molecules to combat <italic>Salmonella</italic> infection.</p>