RT Journal Article SR Electronic T1 DAF-16 and SMK-1 Contribute to Innate Immunity During Adulthood in Caenorhabditis elegans JF G3: Genes|Genomes|Genetics FD Genetics Society of America SP 1521 OP 1539 DO 10.1534/g3.120.401166 VO 10 IS 5 A1 McHugh, Daniel R. A1 Koumis, Elena A1 Jacob, Paul A1 Goldfarb, Jennifer A1 Schlaubitz-Garcia, Michelle A1 Bennani, Safae A1 Regan, Paul A1 Patel, Prem A1 Youngman, Matthew J. YR 2020 UL http://www.g3journal.org/content/10/5/1521.abstract AB Aging is accompanied by a progressive decline in immune function termed “immunosenescence”. Deficient surveillance coupled with the impaired function of immune cells compromises host defense in older animals. The dynamic activity of regulatory modules that control immunity appears to underlie age-dependent modifications to the immune system. In the roundworm Caenorhabditis elegans levels of PMK-1 p38 MAP kinase diminish over time, reducing the expression of immune effectors that clear bacterial pathogens. Along with the PMK-1 pathway, innate immunity in C. elegans is regulated by the insulin signaling pathway. Here we asked whether DAF-16, a Forkhead box (FOXO) transcription factor whose activity is inhibited by insulin signaling, plays a role in host defense later in life. While in younger C. elegans DAF-16 is inactive unless stimulated by environmental insults, we found that even in the absence of acute stress the transcriptional activity of DAF-16 increases in an age-dependent manner. Beginning in the reproductive phase of adulthood, DAF-16 upregulates a subset of its transcriptional targets, including genes required to kill ingested microbes. Accordingly, DAF-16 has little to no role in larval immunity, but functions specifically during adulthood to confer resistance to bacterial pathogens. We found that DAF-16-mediated immunity in adults requires SMK-1, a regulatory subunit of the PP4 protein phosphatase complex. Our data suggest that as the function of one branch of the innate immune system of C. elegans (PMK-1) declines over time, DAF-16-mediated immunity ramps up to become the predominant means of protecting adults from infection, thus reconfiguring immunity later in life.