A conserved role for a GATA transcription factor in regulating epithelial innate immune responses

Michael Shapira; Brigham J. Hamlin; Jiming Rong; Karen Chen; Michal Ronen; Man-Wah Tan

doi:10.1073/pnas.0603424103

New Research In

Edited by Frederick M. Ausubel, Harvard Medical School, Boston, MA, and approved July 10, 2006 (received for review April 26, 2006)

Abstract

Innate immunity is an ancient and conserved defense mechanism. Although host responses toward various pathogens have been delineated, how these responses are orchestrated in a whole animal is less understood. Through an unbiased genome-wide study performed in Caenorhabditis elegans, we identified a conserved function for endodermal GATA transcription factors in regulating local epithelial innate immune responses. Gene expression and functional RNAi-based analyses identified the tissue-specific GATA transcription factor ELT-2 as a major regulator of an early intestinal protective response to infection with the human bacterial pathogen Pseudomonas aeruginosa. In the adult worm, ELT-2 is required specifically for infection responses and survival on pathogen but makes no significant contribution to gene expression associated with intestinal maintenance or to resistance to cadmium, heat, and oxidative stress. We further demonstrate that this function is conserved, because the human endodermal transcription factor GATA6 has a protective function in lung epithelial cells exposed to P. aeruginosa. These findings expand the repertoire of innate immunity mechanisms and illuminate a yet-unknown function of endodermal GATA proteins.

Footnotes

^‡To whom correspondence should be addressed. E-mail: mwtan{at}stanford.edu
Author contributions: M.S. and M.-W.T. designed research; M.S., B.J.H., J.R., K.C., and M.-W.T. performed research; M.S., B.J.H., K.C., M.R., and M.-W.T. contributed new reagents/analytic tools; M.S., K.C., M.R., and M.-W.T. analyzed data; and M.S. and M.-W.T. wrote the paper.
The authors declare no conflict of interest.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The microarray data have been deposited in the Stanford Microarray Database (http://smd.stanford.edu) and the Gene Expression Omnibus database (accession no. GSE5584).
Abbreviations:
DUF,
domain of uncharacterized function;
Esp,
enhanced susceptibility to pathogens;
qRT-PCR,
quantitative RT-PCR;
CUB,
complement subcomponents C1s/C1r, Uegf, Bmp1
Freely available online through the PNAS open access option.
© 2006 by The National Academy of Sciences of the USA