The DAF-16/FOXO transcription factor functions as a regulator of epidermal innate immunity

• Published in: PLoS pathogens 2013-10, Vol.9 (10), p.e1003660-e1003660
• Main Authors: Zou, Cheng-Gang, Tu, Qiu, Niu, Jie, Ji, Xing-Lai, Zhang, Ke-Qin
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - immunology; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - immunology; Caenorhabditis elegans Proteins - metabolism; Calcium Signaling - genetics; Calcium Signaling - immunology; Dermatomycoses - genetics; Dermatomycoses - immunology; Dermatomycoses - metabolism; Epidermis - immunology; Epidermis - metabolism; Forkhead Transcription Factors; Fungal infections; Gene expression; Genetic aspects; Gram-Positive Bacterial Infections - genetics; Gram-Positive Bacterial Infections - immunology; Gram-Positive Bacterial Infections - metabolism; GTP-Binding Protein alpha Subunits, Gq-G11 - genetics; GTP-Binding Protein alpha Subunits, Gq-G11 - immunology; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; Health aspects; Host-parasite relationships; Immune system; Immunity, Innate; Insulin; Kinases; Microbiology; Microorganisms; Mutation; Oxidoreductases - genetics; Oxidoreductases - immunology; Oxidoreductases - metabolism; Physiological aspects; Reactive Oxygen Species - immunology; Reactive Oxygen Species - metabolism; Skin Diseases, Bacterial - genetics; Skin Diseases, Bacterial - immunology; Skin Diseases, Bacterial - metabolism; Staphylococcus infections; Transcription factors; Transcription Factors - genetics; Transcription Factors - immunology; Transcription Factors - metabolism; Worms
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003660

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.