Insulin signaling and the heat shock response modulate protein homeostasis in the Caenorhabditis elegans intestine during infection.
During infection, damage can occur to the host as an outcome of both pathogen virulence mechanisms and host defense strategies. Using aggregation of a model polyglutamine-containing protein as an indicator in Caenorhabditis elegans, we show that protein damage occurs specifically at the site of the host-pathogen interaction, the intestine, in response to various bacterial pathogens. We demonstrate that the insulin signaling pathway and the heat shock transcription factor (HSF-1) influence the amount of aggregation that occurs, in addition to heat shock proteins and oxidative stress enzymes. We also show that addition of the antioxidants epigallocatechin gallate and alpha-lipoic acid reduces polyglutamine aggregation. The influence of oxidative stress enzymes and exogenous antioxidants on protein aggregation suggests that reactive oxygen species produced by the host are a source of protein damage during infection. We propose a model in which heat shock proteins and oxidative stress enzymes regulated by insulin signaling and HSF-1 are required for tissue protection during infection, to minimize the effects of protein damage occurring as a result of host-pathogen interactions.
Mohri-Shiomi
Akiko
A
Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, Texas 77030.
Garsin
Danielle A
DA
Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, Texas 77030. Electronic address: Danielle.A.Garsin@uth.tmc.edu.
D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000494:pharmacology; D001419:Bacteria / Q000254:growth & development; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D006358:Hot Temperature; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000378:metabolism / Q000382:microbiology; D009474:Neurons / Q000378:metabolism / Q000382:microbiology; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D008063:Thioctic Acid / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D000975:Antioxidants; D001426:Bacterial Proteins; D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D008164:Luminescent Proteins; D010455:Peptides; D014157:Transcription Factors; C474710:heat shock factor-1, C elegans; C054562:yellow fluorescent protein, Bacteria; C097188:polyglutamine; D008063:Thioctic Acid; D002392:Catechin; C045651:epigallocatechin gallate