Cultivation of Heligmosomoides Polygyrus: An Immunomodulatory Nematode Parasite and its Secreted Products

Heligmosomoides polygyrus (formerly known as Nematospiroides dubius, and also referred to by some as H. bakeri) is a gastrointestinal helminth that employs multiple immunomodulatory mechanisms to establish chronic infection in mice and closely resembles prevalent human helminth infections. H. polygyrus has been studied extensively in the field of helminth-derived immune regulation and has been found to potently suppress experimental models of allergy and autoimmunity (both with active infection and isolated secreted products). The protocol described in this paper outlines management of the H. polygyrus life cycle for consistent production of L3 larvae, recovery of adult parasites, and collection of their excretory-secretory products (HES).

[1]  S. Akira,et al.  MyD88 Signaling Inhibits Protective Immunity to the Gastrointestinal Helminth Parasite Heligmosomoides polygyrus , 2014, The Journal of Immunology.

[2]  R. Maizels,et al.  Commensal-pathogen interactions in the intestinal tract , 2014, Gut microbes.

[3]  R. Maizels,et al.  Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy , 2014, Mucosal Immunology.

[4]  R. Maizels,et al.  Innate and adaptive type 2 immune cell responses in genetically controlled resistance to intestinal helminth infection , 2014, Immunology and cell biology.

[5]  R. Maizels,et al.  IL-6 controls susceptibility to helminth infection by impeding Th2 responsiveness and altering the Treg phenotype in vivo , 2013, European journal of immunology.

[6]  S. Hartmann,et al.  Small Intestinal Nematode Infection of Mice Is Associated with Increased Enterobacterial Loads alongside the Intestinal Tract , 2013, PloS one.

[7]  J. Weinstock,et al.  Heligmosomoides polygyrus bakeri Infection Activates Colonic Foxp3+ T Cells Enhancing Their Capacity To Prevent Colitis , 2013, The Journal of Immunology.

[8]  A. Ivens,et al.  Secretion of Protective Antigens by Tissue-Stage Nematode Larvae Revealed by Proteomic Analysis and Vaccination-Induced Sterile Immunity , 2013, PLoS pathogens.

[9]  M. Zaiss,et al.  IL-1β Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity , 2013, PLoS pathogens.

[10]  D. Bleich,et al.  Prevention of type 1 diabetes through infection with an intestinal nematode parasite requires IL-10 in the absence of a Th2-type response , 2012, Mucosal Immunology.

[11]  M. Doligalska,et al.  Heligmosomoides polygyrus: EAE remission is correlated with different systemic cytokine profiles provoked by L4 and adult nematodes. , 2012, Experimental parasitology.

[12]  R. Maizels,et al.  Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus , 2012, European journal of immunology.

[13]  R. Maizels,et al.  Immune modulation and modulators in Heligmosomoides polygyrus infection. , 2012, Experimental parasitology.

[14]  R. Maizels,et al.  Cutting Edge: In the Absence of TGF-β Signaling in T Cells, Fewer CD103+ Regulatory T Cells Develop, but Exuberant IFN-γ Production Renders Mice More Susceptible to Helminth Infection , 2012, The Journal of Immunology.

[15]  S. Hartmann,et al.  Mast cells orchestrate type 2 immunity to helminths through regulation of tissue-derived cytokines , 2012, Proceedings of the National Academy of Sciences.

[16]  R. Maizels,et al.  Heligmosomoides polygyrus Elicits a Dominant Nonprotective Antibody Response Directed against Restricted Glycan and Peptide Epitopes , 2011, The Journal of Immunology.

[17]  T. Geary,et al.  Proteomic Analysis of Excretory-Secretory Products of Heligmosomoides polygyrus Assessed with Next-Generation Sequencing Transcriptomic Information , 2011, PLoS neglected tropical diseases.

[18]  M. Blaxter,et al.  Proteomic analysis of secretory products from the model gastrointestinal nematode Heligmosomoides polygyrus reveals dominance of venom allergen-like (VAL) proteins. , 2011, Journal of proteomics.

[19]  M. Morimoto,et al.  Enhanced protection against Heligmosomoides polygyrus in IL-2 receptor β-chain overexpressed transgenic mice with intestinal mastocytosis. , 2011, The Journal of veterinary medical science.

[20]  Irah L. King,et al.  A Nonredundant Role for IL-21 Receptor Signaling in Plasma Cell Differentiation and Protective Type 2 Immunity against Gastrointestinal Helminth Infection , 2010, The Journal of Immunology.

[21]  Sarah A. Ewing,et al.  Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus , 2010, Inflammatory bowel diseases.

[22]  A. Rudensky,et al.  Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-β pathway , 2010, The Journal of experimental medicine.

[23]  R. Maizels,et al.  Helminth-induced CD 19 1 CD 23 hi B cells modulate experimental allergic and autoimmune inflammation , 2010 .

[24]  N. Arizono,et al.  Immunity-mediated regulation of fecundity in the nematode Heligmosomoides polygyrus – the potential role of mast cells , 2009, Parasitology.

[25]  C. Loddenkemper,et al.  Gastrointestinal nematode infection interferes with experimental allergic airway inflammation but not atopic dermatitis , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[26]  D. Bleich,et al.  Helminth Infection Can Reduce Insulitis and Type 1 Diabetes through CD25- and IL-10-Independent Mechanisms , 2009, Infection and Immunity.

[27]  R. Flavell,et al.  Role of T cell TGF‐β signaling in intestinal cytokine responses and helminthic immune modulation , 2009, European journal of immunology.

[28]  H. Noyes,et al.  Heligmosomoides bakeri: a model for exploring the biology and genetics of resistance to chronic gastrointestinal nematode infections , 2009, Parasitology.

[29]  B. Ryffel,et al.  Toll‐like receptor 4 agonists adsorbed to aluminium hydroxide adjuvant attenuate ovalbumin‐specific allergic airway disease: role of MyD88 adaptor molecule and interleukin‐12/interferon‐γ axis , 2008, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[30]  J. Urban,et al.  Anti-Inflammatory Mechanisms of Enteric Heligmosomoides polygyrus Infection against Trinitrobenzene Sulfonic Acid-Induced Colitis in a Murine Model , 2008, Infection and Immunity.

[31]  C. Piccirillo,et al.  Impairment of dendritic cell function by excretory‐secretory products: A potential mechanism for nematode‐induced immunosuppression , 2007, European journal of immunology.

[32]  M. Kurrer,et al.  IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo. , 2007, Blood.

[33]  A. Cooke,et al.  Inhibition of Autoimmune Type 1 Diabetes by Gastrointestinal Helminth Infection , 2006, Infection and Immunity.

[34]  J. Kline,et al.  Intestinal Helminths Protect in a Murine Model of Asthma1 , 2006, The Journal of Immunology.

[35]  F. Iraqi,et al.  Genetic variation in resistance to repeated infections with Heligmosomoides polygyrus bakeri, in inbred mouse strains selected for the mouse genome project , 2006, Parasite immunology.

[36]  R. Maizels,et al.  Suppression of allergic airway inflammation by helminth-induced regulatory T cells , 2005, The Journal of experimental medicine.

[37]  K. Hayes,et al.  Immune‐mediated regulation of chronic intestinal nematode infection , 2004, Immunological reviews.

[38]  A. Sharpe,et al.  The Role of OX40 Ligand Interactions in the Development of the Th2 Response to the Gastrointestinal Nematode Parasite Heligmosomoides polygyrus1 2 , 2003, The Journal of Immunology.

[39]  P. Andersen,et al.  An Enteric Helminth Infection Protects Against an Allergic Response to Dietary Antigen1 , 2002, The Journal of Immunology.

[40]  A. Sharpe,et al.  Memory Th2 Effector Cells Can Develop in the Absence of B7-1/B7-2, CD28 Interactions, and Effector Th Cells After Priming with an Intestinal Nematode Parasite1 , 2002, The Journal of Immunology.

[41]  F. Finkelman,et al.  B7-2 is required for the progression but not the initiation of the type 2 immune response to a gastrointestinal nematode parasite. , 1999, Journal of immunology.

[42]  S. Zhong,et al.  Heligmosomoides polygyrus: resistance in inbred, outbred, and selected mice. , 1996, Experimental parasitology.

[43]  D. Pritchard,et al.  Immunosuppressive proteins secreted by the gastrointestinal nematode parasite Heligmosomoides polygyrus. , 1994, International journal for parasitology.

[44]  F. Enriquez,et al.  Heligmosomoides polygyrus: a model for chronic gastrointestinal helminthiasis. , 1992, Parasitology today.

[45]  W. Paul,et al.  Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[46]  J. Behnke,et al.  Genetic control of immunity to Nematospiroides dubius: a 9‐day anthelmintic abbreviated immunizing regime which separates weak and strong responder strains of mice , 1985, Parasite immunology.

[47]  G. Mitchell,et al.  On the choice of mice for dissection of strain variations in the development of resistance to infection with Nematospiroides dubius. , 1980, The Australian journal of experimental biology and medical science.