title: New Role of Nod Proteins in Regulation of Intestinal Goblet Cell Response in the Context of Innate Host Defense in an Enteric Parasite Infection.
abstract: Mucins secreted by intestinal goblet cells are considered an important component of innate defense in a number of enteric infections, including many parasitic infections, but also likely provide protection against the gut microbiota. Nod proteins are intracellular receptors that play key roles in innate immune response and inflammation. Here, we investigated the role of Nod proteins in regulation of intestinal goblet cell response in naive mice and mice infected with the enteric parasite Trichuris muris. We observed significantly fewer periodic acid-Schiff (PAS)-stained intestinal goblet cells and less mucin (Muc2) in Nod1 and Nod2 double-knockout (Nod DKO) mice after T. muris infection than in wild-type (WT) mice. Expulsion of parasites from the intestine was significantly delayed in Nod DKO mice. Treatment of naive WT mice with Nod1 and Nod2 agonists simultaneously increased numbers of PAS-stained goblet cells and Muc2-expressing cells, whereas treatment with Nod1 or Nod2 separately had no significant effect. Stimulation of mucin-secreting LS174T cells with Nod1 and Nod2 agonists upregulated core 3 β1,3-N-acetylglucosaminyltransferase (C3GnT; an important enzyme in mucin synthesis) and MUC2. We also observed lower numbers of PAS-stained goblet cells and less Muc2 in germfree mice. Treatment with Nod1 and Nod2 agonists enhanced the production of PAS-stained goblet cells and Muc2 in germfree mice. These data provide novel information on the role of Nod proteins in goblet cell response and Muc2 production in relation to intestinal innate defense.
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Denou
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Amanda
authors.initials: A
authors.lastname: Gallagher
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Thornton
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: M Sharif
authors.initials: MS
authors.lastname: Shajib
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schertzer
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Grencis
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada khanwal@mcmaster.ca.
authors.forename: Waliul I
authors.initials: WI
authors.lastname: Khan
mesh_terms: D000818:Animals; D002460:Cell Line; D002687:Chitin Synthase / Q000378:metabolism; D020397:Goblet Cells / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055262:Mucin-2 / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D014257:Trichuriasis / Q000276:immunology* / Q000469:parasitology; D014258:Trichuris / Q000276:immunology*
chemical_list: C524626:Muc2 protein, mouse; D055262:Mucin-2; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D002687:Chitin Synthase