New Role of Nod Proteins in Regulation of Intestinal Goblet Cell Response in the Context of Innate Host Defense in an Enteric Parasite Infection

Mucinssecreted by intestinal goblet cellsare 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. Nodproteins are intracellular receptorsthat play key roles in innate immune response and inflammation. Here, we investigated the role of Nodproteins in regulation of intestinal goblet cellresponse in naive mice and mice infected with the enteric parasite Trichuris muris. We observed significantly fewer periodic acid-Schiff (PAS)-stained intestinal goblet cellsand less mucin(Muc2) in Nod1and Nod2double-knockout ( NodDKO) mice after T. murisinfection than in wild-type (WT) mice. Expulsion of parasites from the intestine was significantly delayed in NodDKO mice. Treatment of naive WT mice with Nod1and Nod2agonists simultaneously increased numbers of PAS-stained goblet cellsand Muc2-expressing cells, whereas treatment with Nod1or Nod2separately had no significant effect. Stimulation of mucin-secreting LS174T cells with Nod1and Nod2agonists upregulated core 3 β1,3-N-acetylglucosaminyltransferase (C3GnT; an important enzyme in mucinsynthesis) and MUC2. We also observed lower numbers of PAS-stained goblet cellsand less Muc2 in germfree mice. Treatment with Nod1and Nod2agonists enhanced the production of PAS-stained goblet cellsand Muc2 in germfree mice. These data provide novel information on the role of Nodproteins in goblet cellresponse and Muc2 production in relation to intestinal innate defense.