Altered expression of goblet cell‐ and mucin glycosylation‐related genes in the intestinal epithelium during infection with the nematode Nippostrongylus brasiliensis in rat

Abstract

Intestinal nematode infection induces marked goblet cell hyperplasia and mucus secretion, but the mechanisms of regulation of the changes still remain to be elucidated. In the present study, epithelial cells were isolated from the rat small intestine at various times after Nippostrongylus brasiliensis infection, and the levels of expression of goblet cell- and mucin glycosylation-related genes were estimated by semi-quantitative reverse transcription (RT)-PCR. Among the genes investigated, mucin core peptide (MUC) 2, sialyltransferase (Siat) 4c and trefoil factor family (TFF) 3 were upregulated as early as 2-4 days post-infection, suggesting that they are associated with an early innate protective response. Seven days post-infection and thereafter, when the nematodes reached maturity, significant upregulation of MUC3, MUC4, resistin-like molecule beta (Relmbeta) and 3O-sulfotransferase (3ST)1 was observed, while 3ST2 expression levels increased after the majority of the worms were expelled from the intestine. Similar alterations of glycosylation-related gene expression were also observed in mast-cell-deficient Ws/Ws rats, suggesting that mast cells in the epithelium are not relevant to the upregulation of these genes. The present finding that the expression level of each goblet cell- or glycosylation-related gene was altered differently during the time course of infection indicates the progression of sequential qualitative changes in the mucus layer after infection.

The mucosal cellular response to infection withAncylostoma ceylanicum

“…Both cell types are known to contain and secrete extremely potent bioactive molecules, and while there has been considerable interest in the role of mast cells in the past, more recently attention has focused on the role of goblet cells. This has been stimulated by the realization that mucus comprises a range of molecules with different properties (Ishikawa et al, 1993), and that the qualities of mucus change during intestinal nematode infections (Yamauchi et al, 2006). Candidate molecules that have been singled out and have attracted attention recently include those among the mucus molecules themselves (Muc2 gene products; Webb et al, 2007) and molecules contained within the mucus (RELMb/ FIZZ2 (Artis et al, 2004) and the lectin encoded by the Intellectin-2 gene (Pemberton et al, 2004;Nair et al, 2006)).…”

A sticky end for gastrointestinal helminths; the role of the mucus barrier

“…spiralis , T. muris and H . polygyrus 76, 77, 78, 79. It has yet to be determined whether these changes occur as a result of the inflammatory environment or to resolve the infection; clearly more research is required to define the precise role of mucin glycans.…”

“…Most of our current understanding of the central role that mucin glycosylation plays during inflammatory threat has come from challenging rodents with infectious agents,71, 77, 78 and there are data to suggest that during GI nematode infections, there are multiple changes in the expression of glycosyltransferases, the enzymes responsible for the synthesis of the glycan chains 75. Yamauchi et al77 have demonstrated that by day 2‐3 of T. spiralis infection, there is an increase in α‐2‐3‐sialyltransferase IV. Additionally, during maturation of T. spiralis, there is also an induction of 3‐0 sulphotransferase‐1 expression in the intestine that peaks at day 14 post‐infection and falls only when parasite expulsion occurs 77.…”

“…Yamauchi et al77 have demonstrated that by day 2‐3 of T. spiralis infection, there is an increase in α‐2‐3‐sialyltransferase IV. Additionally, during maturation of T. spiralis, there is also an induction of 3‐0 sulphotransferase‐1 expression in the intestine that peaks at day 14 post‐infection and falls only when parasite expulsion occurs 77. Furthermore, Dolichos biflorus agglutinin (DBA) and Muc2 dual staining showed a higher prevalence of GalNAc residues on Muc2 in acute T. muris infection compared to chronic infection 10.…”

Toll-Like Receptor 2 andMuc2Expression on Human Intestinal Epithelial Cells by Gymnophalloides seoi Adult Antigen

“…Mucin hypersecretion contributes to expulsion of nematodes and trematodes from the gastrointestinal tract (Nawa et al, 1994;Seo et al, 2003). The expression and regulation of mucin-related (MUC) genes were reported in rodents infected with intestinal nematodes, including Trichinella spiralis and Nippostrongylus brasiliensis (Shekels et al, 2001;Yamauchi et al, 2006).…”