Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions.
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.
Irazoqui
Javier E
JE
Department of Genetics, Harvard Medical School, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ng
Aylwin
A
Xavier
Ramnik J
RJ
Ausubel
Frederick M
FM
D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology*; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D046228:Microarray Analysis; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C477318:Egl-5 protein, C elegans; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D051195:Toll-Like Receptor 2; D014157:Transcription Factors; C115014:bar-1 protein, C elegans; C108831:daf-16 protein, C elegans; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans