4.8 Article

Role for β-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0809527105

Keywords

homeobox protein; host-pathogen interactions; Staphylococcus aureus

Funding

  1. National Institutes of Health [DK43351, DK57521, AI062773, AI064332]
  2. National Center for Research Resources
  3. Jane Coffin Childs Memorial

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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 egi-5 function in parallel to previously described C elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-kappa B-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.

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