Abstract
We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C. elegans beta-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egl-5 function in parallel to previously described C. elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-kappaB-dependent TLR2 signaling in epithelial cells. These data suggest that beta-catenin and homeobox genes play an important and conserved role in innate immune defense.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / immunology*
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Caenorhabditis elegans / microbiology
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / immunology*
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Caenorhabditis elegans Proteins / metabolism
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / immunology*
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Forkhead Transcription Factors
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Homeodomain Proteins / genetics
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Homeodomain Proteins / immunology*
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Intestinal Mucosa / immunology*
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Microarray Analysis
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Mitogen-Activated Protein Kinases / immunology
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Mitogen-Activated Protein Kinases / metabolism
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RNA Interference
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / immunology*
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Staphylococcus aureus / immunology*
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Toll-Like Receptor 2 / immunology
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Toll-Like Receptor 2 / metabolism
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Transcription Factors / metabolism
Substances
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Caenorhabditis elegans Proteins
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Cytoskeletal Proteins
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Egl-5 protein, C elegans
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Forkhead Transcription Factors
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Homeodomain Proteins
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Toll-Like Receptor 2
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Transcription Factors
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bar-1 protein, C elegans
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daf-16 protein, C elegans
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Mitogen-Activated Protein Kinases
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Pmk-1 protein, C elegans