| 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
|
| PII |
PPATHOGENS-D-13-03022
|
| 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
|
|
WOS Category
|
PARASITOLOGY
MICROBIOLOGY
VIROLOGY
|
| Resource |
| C.elegans |
tm2182 |
