Caenorhabditis elegans Innate Immune Response Triggered by Salmonella enterica Requires Intact LPS and Is Mediated by a MAPK Signaling Pathway

Abstract

Compared to mammals, insects, and plants, relatively little is known about innate immune responses in the nematode Caenorhabditis elegans. Previous work showed that Salmonella enterica serovars cause a persistent infection in the C. elegans intestine that triggers gonadal programmed cell death (PCD) and that C. elegans cell death (ced) mutants are more susceptible to Salmonella-mediated killing. To further dissect the role of PCD in C. elegans innate immunity, we identified both C. elegans and S. enterica factors that affect the elicitation of Salmonella-induced PCD. Salmonella-elicited PCD was shown to require the C. elegans homolog of the mammalian p38 mitogen-activated protein kinase (MAPK) encoded by the pmk-1 gene. Inactivation of pmk-1 by RNAi blocked Salmonella-elicited PCD, and epistasis analysis showed that CED-9 lies downstream of PMK-1. Wild-type Salmonella lipopolysaccharide (LPS) was also shown to be required for the elicitation of PCD, as well as for persistence of Salmonella in the C. elegans intestine. However, a presumptive C. elegans TOLL signaling pathway did not appear to be required for the PCD response to Salmonella. These results establish a PMK-1-dependant PCD pathway as a C. elegans innate immune response to Salmonella.

Phage-resistance of Salmonella enterica serovar Enteritidis and pathogenesis in Caenorhabditis elegans is mediated by the lipopolysaccharide

“…It is known that S. Typhimurium requires an intact O-PS to trigger programmed cell death in C. elegans and consequently kill the worm (Aballay et al 2001;Aballay et al 2003). This last study is in agreement with our observations that the S. Enteritidis phage-resistant mutants with an incomplete O-PS (Figure 3) fail to kill C. elegans (Figure 2).…”

Genome-wide RNAi identifies p53-dependent and -independent regulators of germ cell apoptosis in C. elegans

“…18 The worm p38 PMK-1 has been implicated in stress responses and innate immunity, whereas the role of PMK-2 and PMK-3 is still unclear. [18][19][20] Contrary to the pmk-3(lf) Gla phenotype, knockdown of either pmk-1 or pmk-2 does not increase germ cell death (Figure 2b), suggesting a specific involvement of the PMK-3 isoform of p38 in the protection against germ cell apoptosis. bmk-1 encodes a C. elegans homologue of the BimC kinesin-like motor protein involved in spindle formation.…”

Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response

“…RNA interference (RNAi) inactivation of pmk-1, the gene encoding the p38 MAPK that functions downstream of NSY-1 and SEK-1, also resulted in enhanced susceptibility to killing by bacterial pathogens (11,13), and immunoblot analysis showed diminished activation of PMK-1 in nsy-1 and sek-1 mutants. Furthermore, pathogen-elicited apoptosis in C. elegans depended on PMK-1 signaling (14). The central role that PMK-1 plays in mediating C. elegans pathogen resistance parallels the critical function that its mammalian homolog, p38 MAPK, plays in the mammalian immune response to bacterial lipopolysaccharide and to proinflammatory cytokines (15)(16)(17)(18).…”

“…The requirement of the PMK-1 MAPK pathway for immunity to diverse pathogens [Gram-negative (13,14) and Gram-positive (11) bacteria] suggests that various upstream signaling inputs may converge on PMK-1. To further characterize the C. elegans innate immune response, we sought to identify factors that act upstream of PMK-1.…”