Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway.
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.
Aballay
Alejandro
A
Department of Genetics, Harvard Medical School, Massachusetts General Hospital, 02114, Boston, MA, USA. a.aballay@duke.edu
Drenkard
Eliana
E
Hilbun
Layla R
LR
Ausubel
Frederick M
FM
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000276:immunology* / Q000382:microbiology / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D029968:Escherichia coli Proteins; D007107:Immune System / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D019779:Salmonella enterica
D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C103853:RfaL protein, E coli; C439300:Tol-1 protein, C elegans; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans; D020929:Mitogen-Activated Protein Kinase Kinases; D019998:Racemases and Epimerases; C445301:GmhA protein, E coli; D008025:Ligases