Heligmosomoides polygyrus

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. An excellent description of the life cycle and maintenance is presented on the H.poly blogspot.

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 recently completed a proteomic analysis of these secreted products (Hewitson et al 2011).

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 recently demonstrated that HES can convert naive T cells into Foxp3+ Tregs by activating the TGFβ pathway (Grainger et al 2010).

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 genomic project for H. polygyrus. Updates on these projects, and downloadable files will be available shortly at hpolygyrus.bio.ed.ac.uk.

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 a new 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

Immunological Targets

HES protocol

Proteomic Analysis

Transcriptome

Genome