A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.
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.
Shapira
Michael
M
Departments of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hamlin
Brigham J
BJ
Rong
Jiming
J
Chen
Karen
K
Ronen
Michal
M
Tan
Man-Wah
MW
D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000276:immunology*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D050980:GATA Transcription Factors / Q000276:immunology*; D050993:GATA6 Transcription Factor / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D034622:RNA Interference
D029742:Caenorhabditis elegans Proteins; C094134:ELT-2 protein, C elegans; D050980:GATA Transcription Factors; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human