Expulsion of Trichuris muris is associated with increased expression of angiogenin 4 in the gut and increased acidity of mucins within the goblet cell

Abstract

Background: Trichuris muris in the mouse is an invaluable model for infection of man with the gastrointestinal nematode Trichuris trichiura. Three T. muris isolates have been studied, the Edinburgh (E), the Japan (J) and the Sobreda (S) isolates. The S isolate survives to chronicity within the C57BL/6 host whereas E and J are expelled prior to reaching fecundity. How the S isolate survives so successfully in its host is unclear.

Helminths and intestinal barrier function

“…For instance, N. brasiliensis infection has been associated with reduced expression of the mRNA of the anti-microbial peptides, lysozyme-1 and RegIIIg. 89 In contrast, expulsion of the nematode Trichuris muris from mice was accompanied by increased expression of the anti-microbial peptide, angiogenin-4, 84 with goblet cells identified as a source of angiogenin-4 in the colon of infected mice. 100 Reduced numbers of segmented filamentous bacteria (SFB) in the gut of N. brasiliensis-infected mice have been reported (Table 1): 89 SFB are important stimuli of TH17 cells and should this be a general outcome of infection with helminths, the question arises are there any short or long-term consequences to the host to a reduced TH17-TH1 axis in terms of gut homeostasis or vulnerability to microbial pathogens.…”

“…Stimulated electrogenic ion transport creates a driving force for water movement that can lubricate the epithelial surface and may assist in the expulsion of intestinal helminths: 82 water is important in the physical properties of mucus. 83,84 Intestinal goblet cell hyperplasia is perhaps the most prominent gut characteristic of infection with gastrointestinal parasitic helminths 3,85 and increases in mucin production, type (e.g., Muc5a) and glycosylation can be critical components of the epithelial barrier that aids the expulsion of helminths, such as the nematode N. brasiliensis [86][87][88][89] and the trematode, Echinostoma caproni; 90 indeed, helminths in their own defense may release proteases to degrade mucus. 91 The advent of mucin-gene knockout mice positions the field to unequivocally test the role of mucus in the expulsion of a range of parasitic helminths.…”

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

“…However, it is important to note that as the intestinal tract is such a dynamic and exposed tissue, it is also likely that the mucus gel will contain exfoliated cells from the rapidly turned over epithelial layer, bacterial‐derived products and dietary components, making it difficult to extrapolate which proteins are functionally important. However, proteins with a structural, antimicrobial and regulatory function have been associated with the mucus gel and have been identified to be present during parasitic infection 87, 88, 89, 90, 91. Several nonmucin proteins have also been demonstrated to be present within goblet cell granules within the intestine, including IgG Fc‐gamma‐binding protein (FCGBP), trefoil factor (TTF), chloride channel regulator calcium‐activated‐1 (CLCA1), resistin‐like molecule (RELM)‐β and ZG16,87, 92, 93, 94 but relatively few have been investigated during GI nematode infection.…”

“…However, during T. muris and T. spiralis infection there is an induction of RELM‐β expression, but it appears to play little role in expulsion 87. Additionally, the expression of antimicrobial agents derived from goblet cells, namely angiogenin 4, intelectin‐1 and intelectin‐3, have been associated with T. muris expulsion, but their functional importance has yet to be determined 89, 90, 95…”

Macrobiota — helminths as active participants and partners of the microbiota in host intestinal homeostasis

“…As discussed above, production of type 2 cytokines and activation of Treg cells may in turn dampen type 1 inflammatory responses to intestinal bacteria by modulating both TLR signaling and the production of type 1 cytokines, including IFN-γ. Polarisation of the response in helminth infection also raises levels of the antimicrobial products angiogenin 4 [33] and RegIIIγ in the intestines of mice [34]. …”