Salmonellosis is a common foodborne disease. We previously reported the protection of <i>Caenorhabditis elegans</i> from <i>Salmonella</i> Typhimurium DT104 infection by <i>Lactobacillus zeae</i> LB1. However, the mechanism is not fully understood. <i>C. elegans</i> exhibits behavior plasticity when presented with diverse pathogenic or commensal bacteria. Whether it can exert approach avoidance to <i>S</i>. Typhimurium through altering its neurological activity remains to be determined. In the current study, both the wild type and mutants defective in serotonin or dopamine production of <i>C. elegans</i> were used to investigate olfactory preference of the nematode to <i>L. zeae</i> LB1, DT104, and <i>Escherichia coli</i> OP50 by choice assays, and its resistance to DT104 infection and the protection offered by <i>L. zeae</i> LB1 using a life-span assay. The expression of target genes in <i>C. elegans</i> was also examined by real-time quantitative PCR. Results showed that pre-exposure to <i>L. zeae</i> LB1 did not elicit aversive olfactory behavior of the nematode toward DT104. Both mutants <i>
tph-1</i> and <i>
cat-2</i> succumbed faster than the wild type when infected with DT104. While pre-exposure to <i>L. zeae</i> LB1 significantly increased the survival of both the wild type and mutant <i>
tph-1</i>, it provided no protection to mutant <i>
cat-2</i>. Supplementation of dopamine resulted in both the resistance of mutant <i>
cat-2</i> to <i>S</i>. Typhimurium infection and the protection from <i>L. zeae</i> LB1 to the same mutant. Gene expression data also supported the observations in the life-span assay. These results suggest that both serotonin and dopamine play a positive role in the host defense of <i>C. elegans</i> to <i>S</i>. Typhimurium infection and that the <i>L. zeae</i> LB1 protection is not dependent on modifying olfactory preference of the nematode but mediated by dopamine that may have involved the regulation of
p38-mitogen-activated protein kinase and insulin/insulin-like growth factor signaling pathways.