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. 1995 Feb;63(2):591–595. doi: 10.1128/iai.63.2.591-595.1995

High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi-infected pregnant mice and increased TNF-alpha gene transcription in their offspring.

M T Rivera 1, S Marques de Araujo 1, R Lucas 1, J Deman 1, C Truyens 1, M P Defresne 1, P de Baetselier 1, Y Carlier 1
PMCID: PMC173037  PMID: 7822027

Abstract

Since tumor necrosis factor alpha (TNF-alpha) is known to be involved in the feto-maternal relationship, this cytokine was studied in Trypanosoma cruzi-infected pregnant BALB/c mice and their fetuses and offspring. Pregnant chronically infected mice displayed significantly higher levels of circulating TNF-alpha than animals either only infected or only pregnant. TNF-alpha was undetectable in sera of uninfected and nonpregnant mice as well as in breast milk obtained from infected and uninfected animals. Fetuses from infected mice exhibited significantly more cells containing TNF-alpha mRNA in their thymus than fetuses from uninfected mothers. When infected 2 months after birth, offspring born to infected and uninfected mothers displayed similar amounts of circulating TNF-alpha during chronic infection, whereas this cytokine was only weakly detectable during the acute phase of the disease. An intravenous injection of lipopolysaccharide during acute infection strongly increased the production of TNF-alpha in offspring born to infected mothers to levels higher than those in progeny from uninfected mice. These results suggest that TNF-alpha is an important cytokine in the feto-maternal relationship during T. cruzi infection and that fetuses and offspring of infected mothers are primed to produce elevated levels of TNF-alpha.

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Selected References

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  1. Akira S., Taga T., Kishimoto T. Interleukin-6 in biology and medicine. Adv Immunol. 1993;54:1–78. doi: 10.1016/s0065-2776(08)60532-5. [DOI] [PubMed] [Google Scholar]
  2. Bate C. A., Taverne J., Playfair J. H. Soluble malarial antigens are toxic and induce the production of tumour necrosis factor in vivo. Immunology. 1989 Apr;66(4):600–605. [PMC free article] [PubMed] [Google Scholar]
  3. Black C. M., Israelski D. M., Suzuki Y., Remington J. S. Effect of recombinant tumour necrosis factor on acute infection in mice with Toxoplasma gondii or Trypanosoma cruzi. Immunology. 1989 Dec;68(4):570–574. [PMC free article] [PubMed] [Google Scholar]
  4. Bogdan C., Paik J., Vodovotz Y., Nathan C. Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. J Biol Chem. 1992 Nov 15;267(32):23301–23308. [PubMed] [Google Scholar]
  5. Cabeza Meckert P., Chambo G. J., Laguens R. P. Enfermedad congénita secundaria a la infección crónica del ratón con Trypanosoma cruzi. Modelo experimental de la enfermedad de Chagas congénita. Medicina (B Aires) 1980;40 (Suppl 1):40–44. [PubMed] [Google Scholar]
  6. Carlier Y., Rivera M. T., Truyens C., Ontivero M., Flament J., Van Marck E., de Maertelaer V. Chagas' disease: decreased resistance to Trypanosoma cruzi acquired infection in offspring of infected mice. Am J Trop Med Hyg. 1992 Feb;46(2):116–122. doi: 10.4269/ajtmh.1992.46.116. [DOI] [PubMed] [Google Scholar]
  7. Carlier Y., Rivera M. T., Truyens C., Puissant F., Milaire J. Interactions between chronic murine Trypanosoma cruzi infection and pregnancy: fetal growth retardation. Am J Trop Med Hyg. 1987 Nov;37(3):534–540. doi: 10.4269/ajtmh.1987.37.534. [DOI] [PubMed] [Google Scholar]
  8. Chen H. L., Yang Y. P., Hu X. L., Yelavarthi K. K., Fishback J. L., Hunt J. S. Tumor necrosis factor alpha mRNA and protein are present in human placental and uterine cells at early and late stages of gestation. Am J Pathol. 1991 Aug;139(2):327–335. [PMC free article] [PubMed] [Google Scholar]
  9. Clark I. A., Chaudhri G. Tumor necrosis factor in malaria-induced abortion. Am J Trop Med Hyg. 1988 Sep;39(3):246–249. doi: 10.4269/ajtmh.1988.39.246. [DOI] [PubMed] [Google Scholar]
  10. De Titto E. H., Catterall J. R., Remington J. S. Activity of recombinant tumor necrosis factor on Toxoplasma gondii and Trypanosoma cruzi. J Immunol. 1986 Aug 15;137(4):1342–1345. [PubMed] [Google Scholar]
  11. De Togni P., Goellner J., Ruddle N. H., Streeter P. R., Fick A., Mariathasan S., Smith S. C., Carlson R., Shornick L. P., Strauss-Schoenberger J. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994 Apr 29;264(5159):703–707. doi: 10.1126/science.8171322. [DOI] [PubMed] [Google Scholar]
  12. Defresne M. P., Humblet C., Rongy A. M., Greimers R., Boniver J. Effect of interferon-gamma and tumor necrosis factor-alpha on lymphoepithelial interactions within thymic nurse cells. Eur J Immunol. 1990 Feb;20(2):429–432. doi: 10.1002/eji.1830200229. [DOI] [PubMed] [Google Scholar]
  13. Deman J., Martin M. T., Delvenne P., Humblet C., Boniver J., Defresne M. P. Analysis by in situ hybridization of cells expressing mRNA for tumor-necrosis factor in the developing thymus of mice. Dev Immunol. 1992;2(2):103–109. doi: 10.1155/1992/48713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Giroir B. P., Brown T., Beutler B. Constitutive synthesis of tumor necrosis factor in the thymus. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4864–4868. doi: 10.1073/pnas.89.11.4864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Golden J. M., Tarleton R. L. Trypanosoma cruzi: cytokine effects on macrophage trypanocidal activity. Exp Parasitol. 1991 May;72(4):391–402. doi: 10.1016/0014-4894(91)90085-b. [DOI] [PubMed] [Google Scholar]
  16. Gresser I., Woodrow D., Moss J., Maury C., Tavernier J., Fiers W. Toxic effects of recombinant tumor necrosis factor in suckling mice. Comparisons with interferon alpha/beta. Am J Pathol. 1987 Jul;128(1):13–18. [PMC free article] [PubMed] [Google Scholar]
  17. Leite-de-Moraes M. C., Hontebeyrie-Joskowicz M., Dardenne M., Savino W. Modulation of thymocyte subsets during acute and chronic phases of experimental Trypanosoma cruzi infection. Immunology. 1992 Sep;77(1):95–98. [PMC free article] [PubMed] [Google Scholar]
  18. Lucas R., Heirwegh K., Neirynck A., Remels L., Van Heuverswyn H., De Baetselier P. Generation and characterization of a neutralizing rat anti-rmTNF-alpha monoclonal antibody. Immunology. 1990 Oct;71(2):218–223. [PMC free article] [PubMed] [Google Scholar]
  19. MCBURNEY J. J., MEIER H., HOAG W. G. DEVICE FOR MILKING MICE. J Lab Clin Med. 1964 Sep;64:485–487. [PubMed] [Google Scholar]
  20. Magez S., Lucas R., Darji A., Songa E. B., Hamers R., De Baetselier P. Murine tumour necrosis factor plays a protective role during the initial phase of the experimental infection with Trypanosoma brucei brucei. Parasite Immunol. 1993 Nov;15(11):635–641. doi: 10.1111/j.1365-3024.1993.tb00577.x. [DOI] [PubMed] [Google Scholar]
  21. Medlock E. S., Kaplan D. L., Cecchini M., Ulich T. R., del Castillo J., Andresen J. Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis. Blood. 1993 Feb 15;81(4):916–922. [PubMed] [Google Scholar]
  22. Muñoz-Fernández M. A., Fernández M. A., Fresno M. 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):301–307. doi: 10.1002/eji.1830220203. [DOI] [PubMed] [Google Scholar]
  23. Ohsawa T., Natori S. Expression of tumor necrosis factor at a specific developmental stage of mouse embryos. Dev Biol. 1989 Oct;135(2):459–461. doi: 10.1016/0012-1606(89)90194-2. [DOI] [PubMed] [Google Scholar]
  24. Silva J. S., Morrissey P. J., Grabstein K. H., Mohler K. M., Anderson D., Reed S. G. Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. J Exp Med. 1992 Jan 1;175(1):169–174. doi: 10.1084/jem.175.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Starobinas N., Russo M., Minoprio P., Hontebeyrie-Joskowicz M. Is TNF alpha involved in early susceptibility of Trypanosoma cruzi-infected C3H/He mice? Res Immunol. 1991 Feb;142(2):117–122. doi: 10.1016/0923-2494(91)90019-f. [DOI] [PubMed] [Google Scholar]
  26. Suda T., Murray R., Guidos C., Zlotnik A. Growth-promoting activity of IL-1 alpha, IL-6, and tumor necrosis factor-alpha in combination with IL-2, IL-4, or IL-7 on murine thymocytes. Differential effects on CD4/CD8 subsets and on CD3+/CD3- double-negative thymocytes. J Immunol. 1990 Apr 15;144(8):3039–3045. [PubMed] [Google Scholar]
  27. Tarleton R. L. Tumour necrosis factor (cachectin) production during experimental Chagas' disease. Clin Exp Immunol. 1988 Aug;73(2):186–190. [PMC free article] [PubMed] [Google Scholar]
  28. Truyens C., Angelo-Barrios A., Torrico F., Van Damme J., Heremans H., Carlier Y. Interleukin-6 (IL-6) production in mice infected with Trypanosoma cruzi: effect of its paradoxical increase by anti-IL-6 monoclonal antibody treatment on infection and acute-phase and humoral immune responses. Infect Immun. 1994 Feb;62(2):692–696. doi: 10.1128/iai.62.2.692-696.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Van Voorhis W. C. Coculture of human peripheral blood mononuclear cells with Trypanosoma cruzi leads to proliferation of lymphocytes and cytokine production. J Immunol. 1992 Jan 1;148(1):239–248. [PubMed] [Google Scholar]
  30. Wirth J. J., Kierszenbaum F. Recombinant tumor necrosis factor enhances macrophage destruction of Trypanosoma cruzi in the presence of bacterial endotoxin. J Immunol. 1988 Jul 1;141(1):286–288. [PubMed] [Google Scholar]
  31. Yelavarthi K. K., Chen H. L., Yang Y. P., Cowley B. D., Jr, Fishback J. L., Hunt J. S. Tumor necrosis factor-alpha mRNA and protein in rat uterine and placental cells. J Immunol. 1991 Jun 1;146(11):3840–3848. [PubMed] [Google Scholar]
  32. de Kossodo S., Grau G. E., Daneva T., Pointaire P., Fossati L., Ody C., Zapf J., Piguet P. F., Gaillard R. C., Vassalli P. Tumor necrosis factor alpha is involved in mouse growth and lymphoid tissue development. J Exp Med. 1992 Nov 1;176(5):1259–1264. doi: 10.1084/jem.176.5.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]

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