Role for β-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions
- aDepartment of Genetics, Harvard Medical School, and
- bDepartment of Molecular Biology and
- cCenter for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114
-
Contributed by Frederick M. Ausubel, September 24, 2008 (received for review August 8, 2008)
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 β-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-κB-dependent TLR2 signaling in epithelial cells. These data suggest that β-catenin and homeobox genes play an important and conserved role in innate immune defense.
Footnotes
- 1To whom correspondence should be addressed at: Department of Molecular Biology, Massachusetts General Hospital, Simches Research Building, 185 Cambridge Street CPZN7250, Boston, MA 02114. E-mail: ausubel{at}molbio.mgh.harvard.edu
-
Author contributions: J.E.I., A.N., R.J.X., and F.M.A. designed research; J.E.I. and A.N. performed research; J.E.I. and A.N. analyzed data; and J.E.I., A.N., R.J.X., and F.M.A. wrote the paper.
-
The authors declare no conflict of interest.
-
This article contains supporting information online at www.pnas.org/cgi/content/full/0809527105/DCSupplemental.
- © 2008 by The National Academy of Sciences of the USA
