RRC ID 45832
Author Pukkila-Worley R, Feinbaum RL, McEwan DL, Conery AL, Ausubel FM.
Title The evolutionarily conserved mediator subunit MDT-15/MED15 links protective innate immune responses and xenobiotic detoxification.
Journal PLoS Pathog
Abstract Metazoans protect themselves from environmental toxins and virulent pathogens through detoxification and immune responses. We previously identified a small molecule xenobiotic toxin that extends survival of Caenorhabditis elegans infected with human bacterial pathogens by activating the conserved p38 MAP kinase PMK-1 host defense pathway. Here we investigate the cellular mechanisms that couple activation of a detoxification response to innate immunity. From an RNAi screen of 1,420 genes expressed in the C. elegans intestine, we identified the conserved Mediator subunit MDT-15/MED15 and 28 other gene inactivations that abrogate the induction of PMK-1-dependent immune effectors by this small molecule. We demonstrate that MDT-15/MED15 is required for the xenobiotic-induced expression of p38 MAP kinase PMK-1-dependent immune genes and protection from Pseudomonas aeruginosa infection. We also show that MDT-15 controls the induction of detoxification genes and functions to protect the host from bacteria-derived phenazine toxins. These data define a central role for MDT-15/MED15 in the coordination of xenobiotic detoxification and innate immune responses.
Volume 10(5)
Pages e1004143
Published 2014-5-1
DOI 10.1371/journal.ppat.1004143
PMID 24875643
PMC PMC4038581
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / genetics* Evolution, Molecular* Immunity, Innate / genetics* MAP Kinase Signaling System / physiology Pseudomonas aeruginosa* / genetics RNA Interference Transcription Factors / genetics*
IF 6.218
Times Cited 24
C.elegans tm2182