Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2009 Dec 18;284(51):35580-7. doi: 10.1074/jbc.M109.060905.

Regulation of DAF-16-mediated Innate Immunity in Caenorhabditis elegans.

Author information

1
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

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.

PMID:
19858203
PMCID:
PMC2790988
DOI:
10.1074/jbc.M109.060905
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center