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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis Regulatory Proteins
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Caenorhabditis elegans / immunology*
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Caenorhabditis elegans / microbiology
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Caenorhabditis elegans / physiology
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Cell Death / physiology
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Escherichia coli Proteins*
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Immune System / metabolism
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Ligases / genetics
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Ligases / metabolism
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Lipopolysaccharides / immunology
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Lipopolysaccharides / metabolism*
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MAP Kinase Signaling System*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mitogen-Activated Protein Kinase Kinases / genetics
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism
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Mutation
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Nerve Tissue Proteins
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2
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Racemases and Epimerases / genetics
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Racemases and Epimerases / metabolism
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Salmonella enterica*
Substances
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Apoptosis Regulatory Proteins
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Bacterial Proteins
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Caenorhabditis elegans Proteins
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Ced-9 protein, C elegans
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Escherichia coli Proteins
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Lipopolysaccharides
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Membrane Proteins
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Nerve Tissue Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RfaL protein, E coli
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Tol-1 protein, C elegans
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Mitogen-Activated Protein Kinases
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Pmk-1 protein, C elegans
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Mitogen-Activated Protein Kinase Kinases
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Racemases and Epimerases
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GmhA protein, E coli
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Ligases