Regulation of DAF-16-mediated Innate Immunity in Caenorhabditis elegans.
Activation of the innate immune system results in a rapid microbicidal response against microorganisms, which needs to be fine-tuned because uncontrolled immune responses can lead to infection and cancer, as well as conditions such as Crohn disease, atherosclerosis, and Alzheimer disease. Here we report that excessive activity of the conserved FOXO transcription factor DAF-16 enhances susceptibility to bacterial infections in Caenorhabditis elegans. We found that increased temperature activates not only DAF-16 nuclear import but also a control mechanism involved in DAF-16 nuclear export. The nuclear export of DAF-16 requires heat shock transcription factor HSF-1 and Hsp70/HSP-1. Furthermore, we show that increased expression of the water channel Aquoporin-1 is responsible for the deleterious consequences of excessive DAF-16-mediated immune response. These studies reveal a stress-inducible mechanism involved in the regulation of DAF-16 and indicate that uncontrolled DAF-16 activity and water homeostasis are a cause of the deleterious effects of excessive immune responses.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Varsha
V
Singh
Alejandro
A
Aballay
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002467:Cell Nucleus / Q000276:immunology* / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D018840:HSP70 Heat-Shock Proteins; D014157:Transcription Factors; C116823:aqp-1 protein, C elegans; C108831:daf-16 protein, C elegans; C474710:heat shock factor-1, C elegans; D051398:Aquaporin 1