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PMID: 15664955 Published · ppublish English Journal Article

Localized multigene expression patterns support an evolving Th1/Th2-like paradigm in response to infections with Toxoplasma gondii and Ascaris suum.

Infection and immunity ·Vol. 73 ·No. 2 ·2005-02-00 ·Pages 1116-28

Dawson HD, Beshah E, Nishi S, Solano-Aguilar G, Morimoto M, Zhao A, Madden KB, Ledbetter TK, Dubey JP, Shea-Donohue T, Lunney JK, Urban JF

Abstract

Human infectious diseases have been studied in pigs because the two species have common microbial, parasitic, and zoonotic organisms, but there has been no systematic evaluation of cytokine gene expression in response to infectious agents in porcine species. In this study, pigs were inoculated with two clinically and economically important parasites, Toxoplasma gondii and Ascaris suum, and gene expression in 11 different tissues for 20 different swine Th1/Th2-related cytokines, cytokine receptors, and markers of immune activation were evaluated by real-time PCR. A generalized Th1-like pattern of gene expression was evident in pigs infected with T. gondii, along with an increased anti-inflammatory gene expression pattern during the recovery phase of the infection. In contrast, an elevated Th2-like pattern was expressed during the period of expulsion of A. suum fourth-stage larvae from the small intestine of pigs, along with low-level Th1-like and anti-inflammatory cytokine gene expression. Prototypical immune and physiological markers of infection were observed in bronchial alveolar lavage cells, small intestinal smooth muscle, and epithelial cells. This study validated the use of a robust quantitative gene expression assay to detect immune and inflammatory markers at multiple host tissue sites, enhanced the definition of two important swine diseases, and supported the use of swine as an experimental model for the study of immunity to infectious agents relevant to humans.

MeSH Terms
Animals Ascariasis/genetics,immunology,metabolism Ascaris suum/metabolism Cytokines/metabolism Disease Models, Animal Gene Expression Profiling Intestine, Small/immunology,metabolism,parasitology Lung/immunology,metabolism,parasitology RNA, Messenger/metabolism Swine T-Lymphocyte Subsets/immunology Th1 Cells/immunology Th2 Cells/immunology Toxoplasma/metabolism Toxoplasmosis/genetics,immunology,metabolism
Chemicals
Cytokines RNA, Messenger
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Dawson Harry D
Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, US Dept. of Agriculture, Bldg. 307C, Room 214, BARC-East, Beltsville, MD 20705, USA.
Beshah Ethiopia
Nishi Sandra
Solano-Aguilar Gloria
Morimoto Motoko
Zhao Aiping
Madden Kathleen B
Ledbetter Tonya K
Dubey J P
Shea-Donohue Terez
Lunney Joan K
Urban Joseph F
References (64)
64 references, click to expand
  1. Susceptibility of interleukin-2-deficient mice to Toxoplasma gondii is associated with a defect in the production of gamma interferon.
    Infect Immun. 2002 Sep;70(9):4757-61 PMID: 12183516
  2. IL-15 prolongs the duration of CD8+ T cell-mediated immunity in mice infected with a vaccine strain of Toxoplasma gondii.
    J Immunol. 1999 Oct 15;163(8):4503-9 PMID: 10510393
  3. Role of STAT6 and mast cells in IL-4- and IL-13-induced alterations in murine intestinal epithelial cell function.
    J Immunol. 2002 Oct 15;169(8):4417-22 PMID: 12370375
  4. Limited effect of recombinant porcine interleukin-12 on porcine lymphocytes due to a low level of IL-12 beta2 receptor.
    Vet Immunol Immunopathol. 2002 Oct 28;89(3-4):133-48 PMID: 12383645
  5. A road less travelled: large animal models in immunological research.
    Nat Rev Immunol. 2003 Jan;3(1):79-84 PMID: 12511878
  6. Dependence of IL-4, IL-13, and nematode-induced alterations in murine small intestinal smooth muscle contractility on Stat6 and enteric nerves.
    J Immunol. 2003 Jul 15;171(2):948-54 PMID: 12847266
  7. Quantitative real-time PCR for equine cytokine mRNA in nondecalcified bone tissue embedded in methyl methacrylate.
    Calcif Tissue Int. 1999 Nov;65(5):378-83 PMID: 10541764
  8. Cell-mediated immunity to Toxoplasma gondii: initiation, regulation and effector function.
    Immunobiology. 1999 Dec;201(2):240-7 PMID: 10631573
  9. Stat6 signaling promotes protective immunity against Trichinella spiralis through a mast cell- and T cell-dependent mechanism.
    J Immunol. 2000 Feb 15;164(4):2046-52 PMID: 10657657
  10. Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons.
    Science. 2000 Apr 7;288(5463):136-40 PMID: 10753117
  11. IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii.
    J Immunol. 2000 May 15;164(10):5375-82 PMID: 10799901
  12. The biology of Stat4 and Stat6.
    Oncogene. 2000 May 15;19(21):2577-84 PMID: 10851056
  13. Identification of STAT4-dependent and independent mechanisms of resistance to Toxoplasma gondii.
    J Immunol. 2000 Sep 1;165(5):2619-27 PMID: 10946290
  14. Human infection with Ascaris lumbricoides is associated with a polarized cytokine response.
    J Infect Dis. 2000 Oct;182(4):1207-13 PMID: 10979919
  15. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.
    Immunity. 2000 Nov;13(5):715-25 PMID: 11114383
  16. Immunopathology of intestinal helminth infection.
    Parasite Immunol. 2000 Dec;22(12):605-12 PMID: 11123752
  17. Quantitation of bovine cytokine mRNA in milk cells of healthy cattle by real-time TaqMan polymerase chain reaction.
    Vet Immunol Immunopathol. 2000 Dec 29;77(3-4):275-87 PMID: 11137125
  18. Cytokine and lymphocyte profiles in miniature swine after oral infection with Toxoplasma gondii oocysts.
    Int J Parasitol. 2001 Feb;31(2):187-95 PMID: 11239939
  19. Three common presentations of ascariasis infection in an urban Emergency Department.
    J Emerg Med. 2001 Feb;20(2):135-9 PMID: 11207407
  20. Cytokine induction as a measure of cutaneous toxicity in primary and immortalized porcine keratinocytes exposed to jet fuels, and their relationship to normal human epidermal keratinocytes.
    Toxicol Lett. 2001 Mar 8;119(3):209-17 PMID: 11246174
  21. The other side of the coin: the protective role of the TH2 cytokines.
    J Allergy Clin Immunol. 2001 May;107(5):772-80 PMID: 11344341
  22. The role of IL-4 in Heligmosomoides polygyrus-induced alterations in murine intestinal epithelial cell function.
    J Immunol. 2001 Aug 15;167(4):2234-9 PMID: 11490010
  23. Toxoplasma gondii infection in the United States: seroprevalence and risk factors.
    Am J Epidemiol. 2001 Aug 15;154(4):357-65 PMID: 11495859
  24. Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines.
    J Immunol. 2001 Oct 15;167(8):4574-84 PMID: 11591786
  25. Cytokine mRNA quantification by real-time PCR.
    J Immunol Methods. 2002 Jan 1;259(1-2):55-64 PMID: 11730841
  26. Expression of inflammatory cytokines and beta-defensin 1 mRNAs in porcine epithelial rests of Malassez in vitro.
    Med Electron Microsc. 2001 Sep;34(3):174-8 PMID: 11793193
  27. An overview of real-time quantitative PCR: applications to quantify cytokine gene expression.
    Methods. 2001 Dec;25(4):386-401 PMID: 11846608
  28. IL-10 is critical for host resistance and survival during gastrointestinal helminth infection.
    J Immunol. 2002 Mar 1;168(5):2383-92 PMID: 11859129
  29. Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic infection by blocking the development of memory CD8+ T cell response.
    J Exp Med. 2002 Jun 3;195(11):1463-70 PMID: 12045244
  30. Role of IFN-gamma in Th1 differentiation: IFN-gamma regulates IL-18R alpha expression by preventing the negative effects of IL-4 and by inducing/maintaining IL-12 receptor beta 2 expression.
    J Immunol. 2002 Jun 15;168(12):6165-72 PMID: 12055229
  31. Visceral larva migrans due to Ascaris suum which presented with eosinophilic pneumonia and multiple intra-hepatic lesions with severe eosinophil infiltration--outbreak in a Japanese area other than Kyushu.
    Intern Med. 2002 Jul;41(7):574-9 PMID: 12132528
  32. Identification of key immune mediators regulating T helper 1 responses in swine.
    Vet Immunol Immunopathol. 2004 Jul;100(1-2):105-11 PMID: 15183000
  33. In vivo recombinant interleukin 2 administration enhances survival against a lethal challenge with Toxoplasma gondii.
    J Immunol. 1985 Dec;135(6):4160-3 PMID: 3877764
  34. Characterization of isolated porcine intestinal mucosal mast cells following infection with Ascaris suum.
    Vet Parasitol. 1988 Sep;29(2-3):143-58 PMID: 2462304
  35. Influence of helminth parasite exposure and strategic application of anthelmintics on the development of immunity and growth of swine.
    J Anim Sci. 1989 Jul;67(7):1668-77 PMID: 2768122
  36. Diagnosis of transplacentally induced toxoplasmosis in pigs.
    Am J Vet Res. 1990 Aug;51(8):1295-9 PMID: 2386331
  37. Experimental models of toxoplasmosis.
    Res Immunol. 1993 Jan;144(1):16-23 PMID: 8451514
  38. Interleukin-12 enhances murine survival against acute toxoplasmosis.
    Infect Immun. 1994 May;62(5):1639-42 PMID: 7909536
  39. Persistence of immunity to toxoplasmosis in pigs vaccinated with a nonpersistent strain of Toxoplasma gondii.
    Am J Vet Res. 1994 Jul;55(7):982-7 PMID: 7978639
  40. Roles of gamma interferon and other cytokines in suppression of the spleen cell proliferative response to concanavalin A and toxoplasma antigen during acute toxoplasmosis.
    Infect Immun. 1995 Mar;63(3):751-6 PMID: 7868243
  41. Toxoplasmosis.
    J Am Vet Med Assoc. 1994 Dec 1;205(11):1593-8 PMID: 7730132
  42. Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.
    Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7307-11 PMID: 7638186
  43. Induction and regulation of IL-15 expression in murine macrophages.
    J Immunol. 1996 Jan 15;156(2):735-41 PMID: 8543827
  44. Different roles for interleukin-4 during the course of Toxoplasma gondii infection.
    Infect Immun. 1996 Mar;64(3):897-904 PMID: 8641798
  45. In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha.
    J Immunol. 1996 Jul 15;157(2):798-805 PMID: 8752931
  46. IL-15 augments CD8+ T cell-mediated immunity against Toxoplasma gondii infection in mice.
    J Immunol. 1996 Sep 1;157(5):2103-8 PMID: 8757333
  47. Role of IL12 in induction of cell-mediated immunity to Toxoplasma gondii.
    Res Immunol. 1995 Sep-Oct;146(7-8):539-45 PMID: 8839159
  48. Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells.
    J Exp Med. 1997 Mar 3;185(5):817-24 PMID: 9120387
  49. Morbidity and mortality due to Ascaris-induced intestinal obstruction.
    Trans R Soc Trop Med Hyg. 1997 Jan-Feb;91(1):31-6 PMID: 9093623
  50. In vivo production and function of IL-12 p40 homodimers.
    J Immunol. 1997 May 1;158(9):4381-8 PMID: 9127002
  51. Morbidity and mortality due to ascariasis: re-estimation and sensitivity analysis of global numbers at risk.
    Trop Med Int Health. 1997 Jun;2(6):519-28 PMID: 9236818
  52. Oocyst-induced murine toxoplasmosis: life cycle, pathogenicity, and stage conversion in mice fed Toxoplasma gondii oocysts.
    J Parasitol. 1997 Oct;83(5):870-82 PMID: 9379292
  53. Experimental Ascaris suum infection in the pig: worm population kinetics following single inoculations with three doses of infective eggs.
    Parasitology. 1997 Oct;115 ( Pt 4):443-52 PMID: 9364572
  54. Bradyzoite-induced murine toxoplasmosis: stage conversion, pathogenesis, and tissue cyst formation in mice fed bradyzoites of different strains of Toxoplasma gondii.
    J Eukaryot Microbiol. 1997 Nov-Dec;44(6):592-602 PMID: 9435131
  55. Ascaris suum prevalence and intensity: an abattoir survey of market hogs in Saskatchewan.
    Vet Parasitol. 1997 Dec 31;73(3-4):309-13 PMID: 9477517
  56. IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis.
    Immunity. 1998 Feb;8(2):255-64 PMID: 9492006
  57. Toxoplasma gondii: kinetics of the dissemination in the host tissues during the acute phase of infection of mice and rats.
    Exp Parasitol. 1998 Sep;90(1):86-94 PMID: 9709034
  58. A quantitative competitive reverse transcription-polymerase chain reaction technique to measure porcine interferon-gamma.
    J Anim Sci. 1998 Aug;76(8):2155-61 PMID: 9734866
  59. Construction of internal cDNA competitors for measuring IL-10 and IL-12 cytokine gene expression in swine.
    Vet Immunol Immunopathol. 1998 Sep 16;65(1):63-74 PMID: 9802577
  60. Natural immunity to Ascaris lumbricoides associated with immunoglobulin E antibody to ABA-1 allergen and inflammation indicators in children.
    Infect Immun. 1999 Feb;67(2):484-9 PMID: 9916049
  61. Functional and quantitative analysis of splenic T cell immune responses following oral toxoplasma gondii infection in mice.
    Exp Parasitol. 1999 Mar;91(3):212-21 PMID: 10072323
  62. Changes in cytokine levels during reactivation of Toxoplasma gondii infection in lungs.
    Infect Immun. 1999 May;67(5):2082-9 PMID: 10225858
  63. Bovine interleukin-12 and modulation of IFNgamma production.
    Vet Immunol Immunopathol. 1999 May;68(2-4):193-207 PMID: 10438320
  64. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems.
    J Mol Endocrinol. 2002 Aug;29(1):23-39 PMID: 12200227
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.73.2.1116-1128.2005
Published
2005-02-00
Pages
1116-28
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC546930
Subset
IM
External Links
PubMed source DOI: 10.1128/IAI.73.2.1116-1128.2005 PMC Full Text View journal details
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