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PMID: 18804113 Published · ppublish English Journal Article Review

Characterisation of effector mechanisms at the host:parasite interface during the immune response to tissue-dwelling intestinal nematode parasites.

International journal for parasitology ·Vol. 39 ·No. 1 ·2009-01-00 ·Pages 13-21

Patel N, Kreider T, Urban JF, Gause WC

Abstract

The protective immune response that develops following infection with many tissue-dwelling intestinal nematode parasites is characterised by elevations in IL-4 and IL-13 and increased numbers of CD4+ T cells, granulocytes and macrophages. These cells accumulate at the site of infection and in many cases can mediate resistance to these large multicellular pathogens. Recent studies suggest novel potential mechanisms mediated by these immune cell populations through their differential activation and ability to stimulate production of novel effector molecules. These newly discovered protective mechanisms may provide novel strategies to develop immunotherapies and vaccines against this group of pathogens. In this review, we will examine recent studies elucidating mechanisms of host protection against three widely-used experimental murine models of tissue-dwelling intestinal nematode parasites: Heligmosomoides polygyrus, Trichuris muris and Trichinella spiralis.

MeSH Terms
Animals Host-Parasite Interactions/immunology Interleukin-13/immunology Interleukin-4/immunology Intestinal Diseases, Parasitic/immunology,parasitology Mice/parasitology Models, Animal Nematospiroides dubius/immunology,physiology Th2 Cells/immunology Trichinella spiralis/immunology,physiology Trichuris/immunology,physiology
Chemicals
Interleukin-13 Interleukin-4
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Patel Nirav
Department of Medicine, UMDNJ - New Jersey Medical School, MSB F639, 185 South Orange Avenue, Newark, NJ 07103, USA.
Kreider Timothy
Urban Joseph F
Gause William C
References (97)
97 references, click to expand
  1. Coordinated control of immunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, and TGF-beta.
    J Immunol. 2007 Jan 15;178(2):1039-47 PMID: 17202367
  2. Induction of differential T-helper-cell responses in mice infected with variants of the parasitic nematode Trichuris muris.
    Infect Immun. 1996 Mar;64(3):791-5 PMID: 8641783
  3. Infection with parasitic nematodes confounds vaccination efficacy.
    Vet Parasitol. 2007 Aug 19;148(1):14-20 PMID: 17587500
  4. Induction of IL-4 expression in CD4(+) T cells by thymic stromal lymphopoietin.
    J Immunol. 2007 Feb 1;178(3):1396-404 PMID: 17237387
  5. IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis.
    J Immunol. 2004 Jan 15;172(2):1139-45 PMID: 14707089
  6. The epithelium takes centre stage in asthma and atopic dermatitis.
    Trends Immunol. 2007 Jun;28(6):248-51 PMID: 17466594
  7. Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites.
    Immunol Rev. 2004 Oct;201:139-55 PMID: 15361238
  8. Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites.
    Nat Med. 2006 Aug;12(8):955-60 PMID: 16892038
  9. Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production.
    J Clin Invest. 2003 Jan;111(2):225-30 PMID: 12531878
  10. Role of eosinophils and neutrophils in innate and adaptive protective immunity to larval strongyloides stercoralis in mice.
    Infect Immun. 2006 Oct;74(10):5730-8 PMID: 16988250
  11. Enteric nematodes induce stereotypic STAT6-dependent alterations in intestinal epithelial cell function.
    J Immunol. 2004 May 1;172(9):5616-21 PMID: 15100305
  12. Coordinated Muc2 and Muc3 mucin gene expression in Trichinella spiralis infection in wild-type and cytokine-deficient mice.
    Dig Dis Sci. 2001 Aug;46(8):1757-64 PMID: 11508679
  13. Macrophage polarization comes of age.
    Immunity. 2005 Oct;23(4):344-6 PMID: 16226499
  14. Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells.
    J Exp Med. 2002 Oct 7;196(7):969-77 PMID: 12370258
  15. IL-4 secreted from individual naive CD4+ T cells acts in an autocrine manner to induce Th2 differentiation.
    Eur J Immunol. 2002 May;32(5):1428-33 PMID: 11981831
  16. Mast cells and macromolecular leak in intestinal immunological reactions. The influence of sex of rats infected with Nippostrongylus brasiliensis.
    Immunology. 1971 Jul;21(1):17-31 PMID: 5105046
  17. Innate immune response mechanisms in the intestinal epithelium: potential roles for mast cells and goblet cells in the expulsion of adult Trichinella spiralis.
    Parasitology. 2008 May;135(6):655-70 PMID: 18413001
  18. RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract.
    Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13596-600 PMID: 15340149
  19. Role of polymorphonuclear neutrophils on infectious complications stemming from Enterococcus faecalis oral infection in thermally injured mice.
    J Immunol. 2008 Mar 15;180(6):4133-8 PMID: 18322224
  20. The in vivo role of stem cell factor (c-kit ligand) on mastocytosis and host protective immunity to the intestinal nematode Trichinella spiralis in mice.
    Parasite Immunol. 1993 Jan;15(1):55-9 PMID: 7679484
  21. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract.
    J Exp Med. 2006 Apr 17;203(4):843-9 PMID: 16606667
  22. The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection.
    Eur J Immunol. 2006 Jul;36(7):1753-63 PMID: 16783848
  23. The immune response to parasitic helminths: insights from murine models.
    Trends Immunol. 2003 May;24(5):269-77 PMID: 12738422
  24. A new mechanism for IL-5-dependent helminth control: neutrophil accumulation and neutrophil-mediated worm encapsulation in murine filariasis are abolished in the absence of IL-5.
    Int Immunol. 2000 Jun;12(6):899-908 PMID: 10837417
  25. The IL-21 receptor augments Th2 effector function and alternative macrophage activation.
    J Clin Invest. 2006 Jul;116(7):2044-55 PMID: 16778988
  26. CCR3 is required for tissue eosinophilia and larval cytotoxicity after infection with Trichinella spiralis.
    J Immunol. 2002 Jun 1;168(11):5730-6 PMID: 12023373
  27. Cytokine profiles of filarial granulomas in jirds infected with Brugia pahangi.
    Filaria J. 2006 Mar 16;5:3 PMID: 16542426
  28. Alternatively activated macrophages differentially express fibronectin and its splice variants and the extracellular matrix protein betaIG-H3.
    Scand J Immunol. 2001 Apr;53(4):386-92 PMID: 11285119
  29. Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-9 neutralization: correlation with worm expulsion in murine nematode infections.
    Infect Immun. 2003 May;71(5):2430-8 PMID: 12704113
  30. Production of eosinophil chemotactic factor by CD8+ T-cells in Toxocara canis-infected mice.
    Parasitol Res. 1998;84(2):136-8 PMID: 9493213
  31. Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis.
    Nature. 2007 Mar 29;446(7135):552-6 PMID: 17322906
  32. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells.
    J Exp Med. 2007 Aug 6;204(8):1837-47 PMID: 17635955
  33. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses.
    Nat Immunol. 2007 Oct;8(10):1086-94 PMID: 17873879
  34. IL-31-IL-31R interactions negatively regulate type 2 inflammation in the lung.
    J Exp Med. 2007 Mar 19;204(3):481-7 PMID: 17353366
  35. Inflammatory responses to migrating Brugia pahangi third-stage larvae.
    Infect Immun. 2006 Apr;74(4):2366-72 PMID: 16552066
  36. Eosinophils and resistance to Trichinella spiralis.
    J Exp Med. 1977 Mar 1;145(3):755-9 PMID: 233913
  37. Lack of interferon-gamma confers impaired neutrophil granulocyte function and imparts prolonged survival of adult filarial worms in murine filariasis.
    Microbes Infect. 2001 Mar;3(3):203-13 PMID: 11358714
  38. A critical role for stem cell factor and c-kit in host protective immunity to an intestinal helminth.
    Int Immunol. 1996 Apr;8(4):559-67 PMID: 8671643
  39. Identification of a novel eosinophil chemotactic cytokine (ECF-L) as a chitinase family protein.
    J Biol Chem. 2000 Jan 14;275(2):1279-86 PMID: 10625674
  40. Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W/Wv mice.
    Infect Immun. 1983 Jul;41(1):445-7 PMID: 6345400
  41. Transient expression of Ym1, a heparin-binding lectin, during developmental hematopoiesis and inflammation.
    J Leukoc Biol. 2002 Jul;72(1):72-82 PMID: 12101265
  42. Host protective immunity to Trichinella spiralis in mice: activation of Th cell subsets and lymphokine secretion in mice expressing different response phenotypes.
    Immunology. 1991 Oct;74(2):329-32 PMID: 1836201
  43. Three different neutrophil subsets exhibited in mice with different susceptibilities to infection by methicillin-resistant Staphylococcus aureus.
    Immunity. 2004 Aug;21(2):215-26 PMID: 15308102
  44. The wound repair response controls outcome to cutaneous leishmaniasis.
    Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15551-6 PMID: 16223880
  45. Gastritis caused by multiple Nematospiroides dubius infections.
    J Parasitol. 1974 Oct;60(5):790-3 PMID: 4473528
  46. Trichuris muris: host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-gamma.
    Exp Parasitol. 1999 Jun;92(2):144-53 PMID: 10366539
  47. Helper T cell differentiation enters a new era: le roi est mort; vive le roi!
    J Exp Med. 2006 Apr 17;203(4):809-12 PMID: 16606679
  48. Adaptation of a nematode parasite to living within the mammalian epithelium.
    J Exp Zool A Comp Exp Biol. 2005 Nov 1;303(11):927-45 PMID: 16217807
  49. The characterization of intraepithelial lymphocytes, lamina propria leukocytes, and isolated lymphoid follicles in the large intestine of mice infected with the intestinal nematode parasite Trichuris muris.
    J Immunol. 2005 Nov 15;175(10):6713-22 PMID: 16272327
  50. New weapons in the war on worms: identification of putative mechanisms of immune-mediated expulsion of gastrointestinal nematodes.
    Int J Parasitol. 2006 May 31;36(6):723-33 PMID: 16620826
  51. Interleukin-9 is involved in host protective immunity to intestinal nematode infection.
    Eur J Immunol. 1997 Oct;27(10):2536-40 PMID: 9368607
  52. Tissue migration capability of larval and adult Brugia pahangi.
    J Parasitol. 2006 Feb;92(1):46-51 PMID: 16629314
  53. Production of an interferon-gamma homologue by an intestinal nematode: functionally significant or interesting artefact?
    Parasitology. 1997;115 Suppl:S101-6 PMID: 9571695
  54. Nippostrongylus brasiliensis: identification of intelectin-1 and -2 as Stat6-dependent genes expressed in lung and intestine during infection.
    Exp Parasitol. 2007 Aug;116(4):458-66 PMID: 17420014
  55. Differential effects of blockade of CD28-B7 on the development of Th1 or Th2 effector cells in experimental leishmaniasis.
    J Immunol. 1994 Nov 1;153(9):4142-8 PMID: 7523517
  56. IL-4 exacerbates anaphylaxis.
    J Immunol. 2003 Apr 1;170(7):3835-42 PMID: 12646651
  57. Amphiregulin, a TH2 cytokine enhancing resistance to nematodes.
    Science. 2006 Dec 15;314(5806):1746 PMID: 17170297
  58. Synergism of gamma interferon and interleukin-5 in the control of murine filariasis.
    Infect Immun. 2003 Dec;71(12):6978-85 PMID: 14638787
  59. Mucosal mast cells and nematode infection: strain-specific differences in mast cell precursor frequency revisited.
    J Helminthol. 2003 Jun;77(2):155-61 PMID: 12756069
  60. Brugian infections in the peritoneal cavities of laboratory mice: kinetics of infection and cellular responses.
    Exp Parasitol. 2002 Apr;100(4):235-47 PMID: 12128050
  61. IL9 leads to airway inflammation by inducing IL13 expression in airway epithelial cells.
    Int Immunol. 2007 Jan;19(1):1-10 PMID: 17101709
  62. Effect of immunostimulatory oligodeoxynucleotides on host responses and the establishment of Brugia pahangi in Mongolian gerbils (Meriones unguiculatus).
    J Parasitol. 2003 Jun;89(3):483-9 PMID: 12880245
  63. Inhibition of adipocyte differentiation by resistin-like molecule alpha. Biochemical characterization of its oligomeric nature.
    J Biol Chem. 2002 Nov 1;277(44):42011-6 PMID: 12189153
  64. Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion.
    Nat Immunol. 2004 Apr;5(4):426-34 PMID: 14991051
  65. Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells.
    J Exp Med. 2007 Feb 19;204(2):253-8 PMID: 17242164
  66. IL-33, a potent inducer of adaptive immunity to intestinal nematodes.
    J Immunol. 2008 Feb 15;180(4):2443-9 PMID: 18250453
  67. The intestinal mast cell response to Trichinella spiralis infection in mast cell-deficient w/wv mice.
    J Parasitol. 1984 Oct;70(5):767-73 PMID: 6512640
  68. FIZZ1 stimulation of myofibroblast differentiation.
    Am J Pathol. 2004 Apr;164(4):1315-26 PMID: 15039219
  69. Interleukin 2 plays a central role in Th2 differentiation.
    Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3880-5 PMID: 15004274
  70. IL-13-mediated worm expulsion is B7 independent and IFN-gamma sensitive.
    J Immunol. 2000 Apr 15;164(8):4250-6 PMID: 10754322
  71. Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice.
    Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):767-72 PMID: 10639154
  72. Mast cells disrupt epithelial barrier function during enteric nematode infection.
    Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7761-6 PMID: 12796512
  73. The morphology of the attachment and probable feeding site of the nematode Trichuris muris (Schrank, 1788) Hall, 1916.
    Can J Zool. 1978 Sep;56(9):1889-905 PMID: 737601
  74. Peripheral CD4 T cells rapidly accumulate at the host: parasite interface during an inflammatory Th2 memory response.
    J Immunol. 2004 Feb 15;172(4):2424-30 PMID: 14764713
  75. Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion.
    Science. 2005 Jun 3;308(5727):1463-5 PMID: 15933199
  76. Depletion of eosinophils by anti-IL-5 monoclonal antibody treatment of mice infected with Trichinella spiralis does not alter parasite burden or immunologic resistance to reinfection.
    J Immunol. 1992 Dec 1;149(11):3642-7 PMID: 1431133
  77. IL-2 and autocrine IL-4 drive the in vivo development of antigen-specific Th2 T cells elicited by nematode parasites.
    J Immunol. 2005 Feb 15;174(4):2242-9 PMID: 15699158
  78. Macrophages in chronic type 2 inflammation have a novel phenotype characterized by the abundant expression of Ym1 and Fizz1 that can be partly replicated in vitro.
    Immunol Lett. 2003 Jan 22;85(2):173-80 PMID: 12527225
  79. Cutting edge: mechanism of enhancement of in vivo cytokine effects by anti-cytokine monoclonal antibodies.
    J Immunol. 2008 Jan 1;180(1):44-8 PMID: 18097002
  80. TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation.
    Annu Rev Immunol. 2007;25:193-219 PMID: 17129180
  81. Signaling through Galphai2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice.
    J Leukoc Biol. 2007 Apr;81(4):1120-6 PMID: 17242370
  82. Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages.
    J Leukoc Biol. 2002 Apr;71(4):597-602 PMID: 11927645
  83. Mechanisms of neonatal mucosal antibody protection.
    J Immunol. 2006 Nov 1;177(9):6256-62 PMID: 17056555
  84. IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo.
    Blood. 2007 Mar 1;109(5):2023-31 PMID: 17077330
  85. Induction of enhanced immunity to intestinal nematodes using IL-9-producing dendritic cells.
    J Immunol. 2006 Feb 15;176(4):2505-11 PMID: 16456011
  86. Enteric expression of the integrin alpha(v)beta(6) is essential for nematode-induced mucosal mast cell hyperplasia and expression of the granule chymase, mouse mast cell protease-1.
    Am J Pathol. 2002 Sep;161(3):771-9 PMID: 12213704
  87. Gastrointestinal parasite and host interactions.
    Curr Opin Gastroenterol. 2004 Jan;20(1):3-9 PMID: 15703613
  88. Human acidic mammalian chitinase erroneously known as eosinophil chemotactic cytokine is not the ortholog of mouse YM1.
    J Immunol. 2005 Aug 15;175(4):2041-2 PMID: 16081765
  89. Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells.
    Nat Immunol. 2005 May;6(5):507-14 PMID: 15821737
  90. T cell-dependent and -independent expression of intestinal epithelial cell-related molecules in rats infected with the nematode Nippostrongylus brasiliensis.
    APMIS. 2007 Mar;115(3):210-7 PMID: 17367466
  91. Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology.
    J Clin Invest. 2002 Jan;109(1):29-39 PMID: 11781348
  92. Mast cells, eosinophils and antibody-mediated cellular cytotoxicity are not critical in resistance to Trichuris muris.
    Parasite Immunol. 1999 Jan;21(1):45-52 PMID: 10081771
  93. Regulatory T cells and infection: a dangerous necessity.
    Nat Rev Immunol. 2007 Nov;7(11):875-88 PMID: 17948021
  94. Protective immune mechanisms in helminth infection.
    Nat Rev Immunol. 2007 Dec;7(12):975-87 PMID: 18007680
  95. Fibrotic disease and the T(H)1/T(H)2 paradigm.
    Nat Rev Immunol. 2004 Aug;4(8):583-94 PMID: 15286725
  96. Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5513-7 PMID: 2062833
  97. Th2 cytokine-induced alterations in intestinal smooth muscle function depend on alternatively activated macrophages.
    Gastroenterology. 2008 Jul;135(1):217-225.e1 PMID: 18471439
Article Info
Journal
International journal for parasitology
Abbr.
Int J Parasitol
ISSN
1879-0135
DOI
10.1016/j.ijpara.2008.08.003
Published
2009-01-00
Epub
2008-00-30
Pages
13-21
Language
English
Region
England
NLM ID
0314024
PMCID
PMC2842902
Subset
IM
Grants
NIAID NIH HHS · R01 AI031678 · United States
NIAID NIH HHS · R01 AI066188-04 · United States
NIAID NIH HHS · R01 AI031678-12 · United States
NIAID NIH HHS · R01 AI066188-05 · United States
NIAID NIH HHS · R01 AI031678-13 · United States
NIAID NIH HHS · R01 AI066188-03 · United States
NIAID NIH HHS · R01 AI031678-14 · United States
NIAID NIH HHS · R01 AI066188 · United States
External Links
PubMed source DOI: 10.1016/j.ijpara.2008.08.003 PMC Full Text View journal details
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