Regulation of DAF-16-mediated innate immunity in Caenorhabditis elegans

Varsha Singh, Alejandro Aballay

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)35580-35587
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number51
DOIs
StatePublished - Dec 18 2009
Externally publishedYes

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Cell Nucleus Active Transport
Caenorhabditis elegans
Innate Immunity
Aquaporins
Immune system
Microorganisms
Transcription Factors
Chemical activation
Bacterial Infections
Crohn Disease
Water
Immune System
Atherosclerosis
Alzheimer Disease
Homeostasis
Temperature
Infection
Neoplasms
heat shock transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Regulation of DAF-16-mediated innate immunity in Caenorhabditis elegans. / Singh, Varsha; Aballay, Alejandro.

In: Journal of Biological Chemistry, Vol. 284, No. 51, 18.12.2009, p. 35580-35587.

Research output: Contribution to journalArticle

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