title: The DAF-16/FOXO transcription factor functions as a regulator of epidermal innate immunity.
abstract: The Caenorhabditis elegans DAF-16 transcription factor is critical for diverse biological processes, particularly longevity and stress resistance. Disruption of the DAF-2 signaling cascade promotes DAF-16 activation, and confers resistance to killing by pathogenic bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. However, daf-16 mutants exhibit similar sensitivity to these bacteria as wild-type animals, suggesting that DAF-16 is not normally activated by these bacterial pathogens. In this report, we demonstrate that DAF-16 can be directly activated by fungal infection and wounding in wild-type animals, which is independent of the DAF-2 pathway. Fungal infection and wounding initiate the Gαq signaling cascade, leading to Ca(2+) release. Ca(2+) mediates the activation of BLI-3, a dual-oxidase, resulting in the production of reactive oxygen species (ROS). ROS then activate DAF-16 through a Ste20-like kinase-1/CST-1. Our results indicate that DAF-16 in the epidermis is required for survival after fungal infection and wounding. Thus, the EGL-30-Ca(2+)-BLI-3-CST-1-DAF-16 signaling represents a previously unknown pathway to regulate epidermal damage response.
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan, China.
authors.forename: Cheng-Gang
authors.initials: CG
authors.lastname: Zou
authors.forename: Qiu
authors.initials: Q
authors.lastname: Tu
authors.forename: Jie
authors.initials: J
authors.lastname: Niu
authors.forename: Xing-Lai
authors.initials: XL
authors.lastname: Ji
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D003881:Dermatomycoses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate; D010088:Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D017192:Skin Diseases, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C479565:Egl-30 protein, C elegans; D051858:Forkhead Transcription Factors; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C544706:Bli-3 protein, C elegans; D010088:Oxidoreductases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11