title: Insulin signaling and the heat shock response modulate protein homeostasis in the Caenorhabditis elegans intestine during infection.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, Texas 77030.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mohri-Shiomi
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Health Science Center, Houston, Texas 77030. Electronic address: Danielle.A.Garsin@uth.tmc.edu.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Garsin
mesh_terms: 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
chemical_list: 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