Innate immunity in C. elegans requires a conserved PMK-1
p38 mitogen-activated protein kinase (MAPK) pathway that regulates the basal and pathogen-induced expression of immune effectors. We identified ATF-7, a conserved basic-region leucine zipper (bZIP) transcription factor, as a downstream target of PMK-1
p38 MAPK and a regulator of immune effector gene expression. Loss of
atf-7 function can partially suppress the enhanced susceptibility to pathogen phenotype conferred by loss of
pmk-1 function by restoring the basal expression of PMK-1-regulated genes. In contrast, the pathogen-induced expression of these genes is not restored by loss of
atf-7 function in a
pmk-1 mutant. This suggests a model in which, when PMK-1
p38 MAPK is inactive, ATF-7 functions as a transcriptional repressor of PMK-1-regulated genes that, during infection, undergoes a switch to a transcriptional activator upon phosphorylation by activated PMK-1
p38 MAPK. To identify other components that regulate the PMK-1
p38 MAPK-dependent immune response, we performed a
pmk-1 suppressor screen. We screened 35,000 haploid genomes and identified 51 mutants that partially suppress the enhanced susceptibility to pathogen phenotype conferred by
pmk-1 loss-of-function. We anticipate that our genetic screen will identify genes that function with
atf-7 and provide insight into the mechanism of the ATF-7-mediated transcriptional control of PMK-1
p38 MAPK-dependent immunity.