The Evolutionarily Conserved Mediator Subunit MDT-15/MED15 Links Protective Innate Immune Responses and Xenobiotic Detoxification

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. © 2014 pukkila-worley et al.