Heligmosomoides polygyrus is a natural nematode parasite of mice. It pursues a direct and entirely enteric life cycle, entering through the mouth and maturing in the intestine to produce eggs which are voided with faeces. It is a valuable laboratory model as it can establish chronic infection in different strains of mice. A detailed description and video of the life cycle and maintenance is available in our open-access Journal of Visualised Experiments article. Additional useful information on the parasite is presented on the H.poly blogspot. General references on the biology and immunology of the parasite include Monroy & Enriquez (1992), Behnke (2009). and Reynolds et al (2012).
H. polygyrus exerts potent immunomodulatory effects on the murine immune system, suppressing airway allergy, autoimmunity and bystander responses to other antigens. Our laboratory has established that many of these effects can be reproduced by H. polygyrus "Excretory-Secretory" (HES) antigens, and we have published proteomic analyses of the adult secreted products (Hewitson et al 2011), and of the secretions of larval stages (Hewitson et al 2013).
Among the most marked effects of H. polygyrus is the activation of Regulatory T cells (Tregs) which are responsible for key outcomes such as suppression of airway allergy (as reported by Wilson et al, 2005). We have demonstrated that HES can convert naive T cells into Foxp3+ Tregs by activating the TGFβ pathway (Grainger et al 2010) through a novel protein termed TGM (TGF-β Mimic) (Johnston et al 2017).
We are also investigating how Tregs are generated in vivo; new work has found that in the mesenteric lymph nodes draining the gut, a novel phenotype of dendritic cells (CD11c-low, CD103-negative) is present which preferentially induces regulatory T cells (Smith et al 2011).
As part of our molecular analysis of HES, we have now identified the major immunological targets recognised by serum antibodies in infected mice, and defined the principal antigens as two glycans (Glycans A and B) and a set of Venom allergen/Ancylostoma secreted protein-Like (VAL) homologues.
Our laboratory is also undertaking, on a collaborative basis, an extensive transcriptomic and genomicproject for H. polygyrus. .
Photograph : at 7 days post-infection, maturing parasites are encysted in the gut wall but will shortly migrate back into the intestinal lumen. (Photograph (c) R M Maizels)
H. polygyrus has had a chequered taxonomic history. Until the late 1980s it was named Nematospiroides dubius, and in 2009 a proposal has been made to rename it again as H. bakeri; however this has not met with widespread agreement, and for reasons set out elsewhere (Maizels et al 2011), we recommend designating the laboratory model as H. polygyrus bakeri.
Life cycle
Immunomodulatory effects
The following table is based on a summary of the immunomodulatory effects of H polygyrus published in Maizels et al (2011) Experimental Parasitology, in press
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Antigen-specific responses
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Antibody to SRBC inhibited in infection
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(Ali and Behnke, 1983; Ali and Behnke, 1984; Shimp et al., 1975)
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Antibody to SRBC inhibited by adult worm homogenate, and by cells from mice given adult worm homogenate
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(Pritchard et al., 1984)
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Antibody to ovalbumin
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(Boitelle et al., 2005)
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Immune cell functions
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Inhibition of DC responses to TLR ligation, and reduction of IL-12 secretion
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(Massacand et al., 2009; Segura et al., 2007)
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Expansion of Foxp3+ CD103+ Tregs
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(Finney et al., 2007; Rausch et al., 2008)
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Induction of bystander (OVA-specific) Foxp3+ Tregs
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(Grainger et al., 2010)
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Autoimmunity
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Inhibits colitis in IL-10-deficient mice
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(Elliott et al., 2004; Hang et al., 2010)
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Inhibits TNBS-induced colitis
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(Sutton et al., 2008)
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Inhibits Type I diabetes
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(Liu et al., 2009; Saunders et al., 2006)
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Allergy
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Inhibits airway allergic inflammation
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(Kitagaki et al., 2006; Wilson et al., 2005)
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Inhibits food allergy
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(Bashir et al., 2002)
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Co-infections
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Reduces liver immunopathological reactions to schistosome eggs
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(Bazzone et al., 2008)
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Exacerbates Plasmodium chabaudi and P. yoeliiinfections, suppressing IFN-γ responses
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(Helmby, 2009; Noland et al., 2008; Su et al., 2005; Tetsutani et al., 2009)
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Aggravates Citrobacter rodentium infection and colitis
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(Chen et al., 2005; Weng et al., 2007)
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Extends Nippostrongylus brasiliensis, Trichuris muris andTrichinella spiralis infections, suppresses IL-9 and mast cell response
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(Behnke et al., 1978; Behnke et al., 1993; Colwell and Wescott, 1973; Dehlawi et al., 1987; Jenkins and Behnke, 1977)
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Modulates Helicobacter pylori-induced inflammation
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(Fox et al., 2000)
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Results in greater Eimeria facliformis proliferation
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(Rausch et al., 2010)
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Inhibits protective CD8+ T cell responses to Toxoplasma gondii
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(Khan et al., 2008)
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Reduced antibody responses to haemagglutinin in influenza A infections
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(Chowaniec et al., 1972)
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Reduces response to malaria and Salmonella vaccination
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(Druilhe et al., 2006; Su et al., 2006; Urban et al., 2007)
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Immunological Targets
Our study of the targets of antibody responsiveness to H. polygyrus infection is summarised in the image above.
HES Protocol
Proteomic Analysis
Our laboratory is actively characterising the components of HES. A summary of the most abundant proteins visible by staining of 2-D gels is presented below. A full analysis is available in Hewitson et al (2011)
Transcriptome
Analysis of the H. polygyrus transcriptome is currently underway in collaboration with the GenePool, University of Edinburgh. A summary of current reads is given above.
Genome
Analysis of the H. polygyrus transcriptome is currently underway in collaboration with the GenePool, University of Edinburgh. A summary of current reads is given below. N50 447 Max_contig_size 13743 Number of bases in contigs 293851723 Number of contigs 714320 Number of contigs >=1kb 24734 Number of contigs >=10kb 2 Number of contigs in N50 208118 Number of bases in contigs >=1kb 32425581 GC Content of contigs 46.1220824626575