title: A UPR-independent infection-specific role for a BiP/GRP78 protein in the control of antimicrobial peptide expression in C. elegans epidermis.
abstract: The nematode C. elegans responds to infection by the fungus Drechmeria coniospora with a rapid increase in the expression of antimicrobial peptide genes. To investigate further the molecular basis of this innate immune response, we took a two-dimensional difference in-gel electrophoresis (2D-DIGE) approach to characterize the changes in host protein that accompany infection. We identified a total of 68 proteins from differentially represented spots and their corresponding genes. Through class testing, we identified functional categories that were enriched in our proteomic data set. One of these was "protein processing in endoplasmic reticulum," pointing to a potential link between innate immunity and endoplasmic reticulum function. This class included HSP-3, a chaperone of the BiP/GRP78 family known to act coordinately in the endoplasmic reticulum with its paralog HSP-4 to regulate the unfolded protein response (UPR). Other studies have shown that infection of C. elegans can provoke a UPR. We observed, however, that in adult C. elegans infection with D. coniospora did not induce a UPR, and conversely, triggering a UPR did not lead to an increase in expression of the well-characterized antimicrobial peptide gene nlp-29. On the other hand, we demonstrated a specific role for hsp-3 in the regulation of nlp-29 after infection that is not shared with hsp-4. Epistasis analysis allowed us to place hsp-3 genetically between the Tribbles-like kinase gene nipi-3 and the protein kinase C delta gene tpa-1. The precise function of hsp-3 has yet to be determined, but these results uncover a hitherto unsuspected link between a BiP/GRP78 family protein and innate immune signaling.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université, Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Couillault
authors.forename: Patrick
authors.initials: P
authors.lastname: Fourquet
authors.forename: Matthieu
authors.initials: M
authors.lastname: Pophillat
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Ewbank
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004817:Epidermis / Q000737:chemistry / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; C502195:Hsp-3 protein, C elegans