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PMID: 9596773 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Trypanosoma cruzi infection in tumor necrosis factor receptor p55-deficient mice.

Infection and immunity ·Vol. 66 ·No. 6 ·1998-06-00 ·Pages 2960-8

Castaños-Velez E, Maerlan S, Osorio LM, Aberg F, Biberfeld P, Orn A, Rottenberg ME

Abstract

Tumor necrosis factor receptor p55 (TNFRp55) mediates host resistance to several pathogens by allowing microbicidal activities of phagocytes. In the studies reported here, TNFRp55-/- mice infected with the intracellular parasite Trypanosoma cruzi showed clearly higher parasitemia and cumulative mortality than wild-type (WT) controls did. However, gamma interferon (IFN-gamma)-activated macrophages from TNFRp55-/- mice produced control levels of nitric oxide and killed the parasite efficiently in vitro. Trypanocidal mechanisms of nonphagocytic cells (myocardial fibroblasts) from both TNFRp55-/- and WT mice were also activated by IFN-gamma in a dose-dependent way. However, IFN-gamma-activated TNFRp55-/- nonphagocytes showed less effective killing of T. cruzi than WT control nonphagocytes, even when interleukin 1beta (IL-1beta) was added as a costimulator. In vivo, T. cruzi-infected TNFRp55-/- mice and WT mice released similar levels of NO and showed similar levels of IFN-gamma mRNA and inducible nitric oxide synthase mRNA in their tissues. Instead, increased susceptibility to T. cruzi of TNFRp55-/- mice was associated with reduced levels of parasite-specific immunoglobulin G (IgG) (but not IgM) antibodies during infection, which is probably linked to abnormal B-cell differentiation in secondary lymphoid tissues of the mutant mice. Surprisingly, T. cruzi-infected TNFRp55-/- mice showed increased inflammatory and necrotic lesions in several tissues, especially in skeletal muscles, indicating that TNFRp55 plays an important role in controlling the inflammatory process. Accordingly, levels of Mn2+ superoxide dismutase mRNA, a TNF-induced enzyme which protects the cell from the toxic effects of superoxide, were lower in mutant than in WT infected mice.

MeSH Terms
Animals Antibodies, Protozoan/blood Antigens, CD/metabolism Chagas Disease/immunology,mortality Disease Susceptibility Fibroblasts/immunology,parasitology Heart/parasitology Immunoglobulin G/blood Immunoglobulin M/blood Interferon-gamma/pharmacology Macrophages, Peritoneal/immunology,parasitology Mice Mice, Mutant Strains Myocardium/cytology Nitrates/blood Nitric Oxide/metabolism Nitric Oxide Synthase/biosynthesis Nitric Oxide Synthase Type II Parasitemia/immunology,mortality Receptors, Tumor Necrosis Factor/metabolism Receptors, Tumor Necrosis Factor, Type I Spleen/pathology Superoxide Dismutase/biosynthesis Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Antibodies, Protozoan Antigens, CD Immunoglobulin G Immunoglobulin M Nitrates Receptors, Tumor Necrosis Factor Receptors, Tumor Necrosis Factor, Type I Tumor Necrosis Factor-alpha Nitric Oxide Interferon-gamma Nitric Oxide Synthase Nitric Oxide Synthase Type II Nos2 protein, mouse Superoxide Dismutase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Castaños-Velez E
Department of Pathology, Karolinska Institute, Stockholm, Sweden.
Maerlan S
Osorio L M
Aberg F
Biberfeld P
Orn A
Rottenberg M E
References (57)
57 references, click to expand
  1. Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice.
    Immunity. 1995 Jun;2(6):561-72 PMID: 7540941
  2. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase.
    Cell. 1995 May 19;81(4):641-50 PMID: 7538909
  3. TNF receptors in murine Candida albicans infection: evidence for an important role of TNF receptor p55 in antifungal defense.
    J Immunol. 1996 Sep 1;157(5):2155-9 PMID: 8757341
  4. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation.
    Cell. 1995 May 19;81(4):495-504 PMID: 7758105
  5. Activity of recombinant tumor necrosis factor on Toxoplasma gondii and Trypanosoma cruzi.
    J Immunol. 1986 Aug 15;137(4):1342-5 PMID: 3525677
  6. Nitric oxide is involved in control of Trypanosoma cruzi-induced parasitemia and directly kills the parasite in vitro.
    Infect Immun. 1994 Nov;62(11):5177-82 PMID: 7523307
  7. Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific.
    Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2830-4 PMID: 1849278
  8. Persistent production of inflammatory and anti-inflammatory cytokines and associated MHC and adhesion molecule expression at the site of infection and disease in experimental Trypanosoma cruzi infections.
    Exp Parasitol. 1996 Nov;84(2):203-13 PMID: 8932770
  9. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor.
    Cell. 1994 Aug 26;78(4):681-92 PMID: 8069916
  10. Competitive PCR.
    Nature. 1992 Oct 8;359(6395):557-8 PMID: 1383831
  11. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production.
    J Immunol. 1988 Oct 1;141(7):2407-12 PMID: 3139757
  12. "Macrophage" nitric oxide synthase is a glucocorticoid-inhibitable primary response gene in 3T3 cells.
    J Cell Physiol. 1993 Oct;157(1):128-32 PMID: 7691832
  13. Corynebacterium parvum- and Mycobacterium bovis bacillus Calmette-Guerin-induced granuloma formation is inhibited in TNF receptor I (TNF-RI) knockout mice and by treatment with soluble TNF-RI.
    J Immunol. 1996 Dec 1;157(11):5022-6 PMID: 8943410
  14. Tumour necrosis factor-alpha in murine autoimmune 'lupus' nephritis.
    Nature. 1988 Jan 28;331(6154):356-8 PMID: 2893286
  15. Evidence for a protective role of tumor necrosis factor in the acute phase of Trypanosoma cruzi infection in mice.
    Infect Immun. 1997 Feb;65(2):457-65 PMID: 9009297
  16. Nitric oxide synthesis in cardiac myocytes and fibroblasts by inflammatory cytokines.
    Cardiovasc Res. 1995 Jun;29(6):813-9 PMID: 7544689
  17. Overexpression of mitochondrial manganese superoxide dismutase promotes the survival of tumor cells exposed to interleukin-1, tumor necrosis factor, selected anticancer drugs, and ionizing radiation.
    FASEB J. 1993 Feb 1;7(2):361-8 PMID: 8440412
  18. Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in scid mice.
    J Immunol. 1989 Jul 1;143(1):127-30 PMID: 2499625
  19. Role of lymphotoxin and the type I TNF receptor in the formation of germinal centers.
    Science. 1996 Mar 1;271(5253):1289-91 PMID: 8638112
  20. Characterization of inflammatory infiltrates in chronic chagasic myocardial lesions: presence of tumor necrosis factor-alpha+ cells and dominance of granzyme A+, CD8+ lymphocytes.
    Am J Trop Med Hyg. 1993 May;48(5):637-44 PMID: 8517482
  21. Trypanosoma cruzi: ability of T-cell-enriched and -depleted lymphocyte populations to passively protect mice.
    Exp Parasitol. 1980 Apr;49(2):225-32 PMID: 6767621
  22. Effects of polyethylene glycol conjugated superoxide dismutase on coxsackievirus B3 myocarditis in mice.
    Cardiovasc Res. 1992 Oct;26(10):956-61 PMID: 1336713
  23. Macrophage activation and resistance to Trypanosoma cruzi infection.
    Res Immunol. 1991 Feb;142(2):144-6 PMID: 1907754
  24. Role of oxygen derived free radicals in the pathogenesis of coxsackievirus B3 myocarditis in mice.
    Cardiovasc Res. 1993 Jun;27(6):957-61 PMID: 8221785
  25. Trypanosoma cruzi: role of the immune response in the natural resistance of inbred strains of mice.
    Exp Parasitol. 1978 Aug;45(2):160-8 PMID: 210036
  26. Tumor necrosis factor receptor p55 mediates deletion of peripheral cytotoxic T lymphocytes in vivo.
    Eur J Immunol. 1996 Dec;26(12):3055-60 PMID: 8977304
  27. Tumour necrosis factor (cachectin) production during experimental Chagas' disease.
    Clin Exp Immunol. 1988 Aug;73(2):186-90 PMID: 3141092
  28. Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist.
    Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3725-9 PMID: 8097322
  29. Recombinant tumor necrosis factor enhances macrophage destruction of Trypanosoma cruzi in the presence of bacterial endotoxin.
    J Immunol. 1988 Jul 1;141(1):286-8 PMID: 3288698
  30. Differentiation of follicular dendritic cells and full antibody responses require tumor necrosis factor receptor-1 signaling.
    J Exp Med. 1996 May 1;183(5):2367-72 PMID: 8642347
  31. The p70 tumor necrosis factor receptor mediates cytotoxicity.
    Cell. 1992 Jul 10;70(1):47-56 PMID: 1320461
  32. Phagocytosis: a defense mechanism against infection with Trypanosoma cruzi.
    J Immunol. 1974 May;112(5):1839-44 PMID: 4361979
  33. The microbicidal activity of interferon-gamma-treated macrophages against Trypanosoma cruzi involves an L-arginine-dependent, nitrogen oxide-mediated mechanism inhibitable by interleukin-10 and transforming growth factor-beta.
    Eur J Immunol. 1992 Oct;22(10):2501-6 PMID: 1396957
  34. The tumor necrosis factor ligand and receptor families.
    N Engl J Med. 1996 Jun 27;334(26):1717-25 PMID: 8637518
  35. [Isolation of a strain of Trypanosoma cruzi from a patient with chronic Chagas cardiomyopathy and its biological characterization].
    Medicina (B Aires). 1980;40 Suppl 1:63-8 PMID: 6779089
  36. Connective tissue reactions in normal and immunized mice to a reticulotropic strain of Trypanosoma cruzi.
    J Infect Dis. 1955 May-Jun;96(3):199-226 PMID: 14392366
  37. Induction of proinflammatory cytokine expression in experimental acute Chagasic cardiomyopathy.
    Biochem Biophys Res Commun. 1996 Jun 14;223(2):365-71 PMID: 8670288
  38. The two different receptors for tumor necrosis factor mediate distinct cellular responses.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9292-6 PMID: 1718003
  39. Increased production of reactive oxygen species by cells from mice acutely infected with Trypanosoma cruzi.
    Cell Immunol. 1990 Jun;128(1):11-21 PMID: 2111736
  40. Killing in vitro of Trypanosoma cruzi by macrophages from mice immunized with T. cruzi or BCG, and absence of cross-immunity on challege in vivo.
    J Exp Med. 1975 Aug 1;142(2):299-311 PMID: 806649
  41. A spectrophotometric assay for nitrate using NADPH oxidation by Aspergillus nitrate reductase.
    Anal Biochem. 1993 Aug 1;212(2):359-65 PMID: 8214577
  42. The cachexia associated with Trypanosoma cruzi acute infection in mice is attenuated by anti-TNF-alpha, but not by anti-IL-6 or anti-IFN-gamma antibodies.
    Parasite Immunol. 1995 Nov;17(11):561-8 PMID: 8817602
  43. Trypanosoma cruzi: cytokine effects on macrophage trypanocidal activity.
    Exp Parasitol. 1991 May;72(4):391-402 PMID: 1902795
  44. Trypanosoma cruzi upregulates nitric oxide release by IFN-gamma-preactivated macrophages, limiting cell infection independently of the respiratory burst.
    Parasite Immunol. 1993 Dec;15(12):693-9 PMID: 7877845
  45. Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism.
    Science. 1988 Nov 11;242(4880):941-4 PMID: 3263703
  46. Effect of recombinant tumour necrosis factor on acute infection in mice with Toxoplasma gondii or Trypanosoma cruzi.
    Immunology. 1989 Dec;68(4):570-4 PMID: 2514141
  47. Trypanosoma cruzi: role of different antibody classes in protection against infection in the mouse.
    Exp Parasitol. 1981 Aug;52(1):137-46 PMID: 6786912
  48. Synergism between tumor necrosis factor-alpha and interferon-gamma on macrophage activation for the killing of intracellular Trypanosoma cruzi through a nitric oxide-dependent mechanism.
    Eur J Immunol. 1992 Feb;22(2):301-7 PMID: 1537373
  49. Role of nitric oxide in resistance and histopathology during experimental infection with Trypanosoma cruzi.
    Immunol Lett. 1995 Jul-Aug;47(1-2):121-6 PMID: 8537088
  50. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection.
    Cell. 1993 May 7;73(3):457-67 PMID: 8387893
  51. Tumor necrosis factor alpha mediates resistance to Trypanosoma cruzi infection in mice by inducing nitric oxide production in infected gamma interferon-activated macrophages.
    Infect Immun. 1995 Dec;63(12):4862-7 PMID: 7591147
  52. Susceptible mice present higher macrophage activation than resistant mice during infections with myotropic strains of Trypanosoma cruzi.
    Parasite Immunol. 1989 Jul;11(4):385-95 PMID: 2528710
  53. Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-alpha.
    J Immunol. 1993 May 1;150(9):3982-9 PMID: 8473745
  54. Intracellular co-localization of Trypanosoma cruzi and inducible nitric oxide synthase (iNOS): evidence for dual pathway of iNOS induction.
    Eur J Immunol. 1996 Dec;26(12):3203-13 PMID: 8977323
  55. Greatly accelerated lymphadenopathy and autoimmune disease in lpr mice lacking tumor necrosis factor receptor I.
    J Immunol. 1996 Apr 15;156(8):2661-5 PMID: 8609380
  56. Mice lacking the TNF receptor p55 fail to resolve lesions caused by infection with Leishmania major, but control parasite replication.
    J Immunol. 1996 Jul 15;157(2):827-35 PMID: 8752935
  57. Mechanisms of resistance against experimental Trypanosoma cruzi infection: the importance of antibodies and antibody-forming capacity in the Biozzi high and low responder mice.
    J Immunol. 1976 May;116(5):1208-11 PMID: 818311
Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.66.6.2960-2968.1998
Published
1998-06-00
Pages
2960-8
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC108295
Subset
IM
External Links
PubMed source DOI: 10.1128/IAI.66.6.2960-2968.1998 PMC Full Text View journal details
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