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.
Highlights
Dauer formation abnormal (DAF)2-16 is a key FOXO transcription factor that controls innate immunity in C. elegans
Further studies indicate that increased expression of the water channel Aquaporin is responsible for the deleterious effects of excessive DAF-16-mediated immune response
Hyperactivation of DAF-16 by Heat Shock Makes C. elegans Susceptible to Pathogen Infection—Increased temperature is an ancient immune mechanism used by metazoans in response to microbial infections
Summary
Dauer formation abnormal (DAF)2-16 is a key FOXO transcription factor that controls innate immunity in C. elegans. P. aeruginosa than daf-16::gfp animals alone, providing further support to the idea that continued nuclear accumulation of DAF-16 has deleterious effects on immune responses against pathogen infections.
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