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. 1978 Jul 1;148(1):288–300. doi: 10.1084/jem.148.1.288

Trypanosoma cruzi: in vitro induction of macrophage microbicidal activity

PMCID: PMC2184909  PMID: 353218

Abstract

Normal, resident and inflammatory mouse peritoneal macrophages can be induced to display microbicidal activity against trypomastigotes of Trypanosoma cruzi by exposure to products from antigen-pulsed, sensitized spleen cell populations. Optimal macrophage microbicidal activity was achieved by constant exposure and daily renewal of the spleen cell factors. Macrophages obtained after an intraperitoneal injection of mild inflammatory agents were rapidly induced, displaying trypanocidal activity 24 h after exposure to the active spleen cell factor(s), and by 48 h, parasites were no longer observed. Resident peritoneal macrophages required 24 h longer for activation. Removal of the factor(s) before achieving complete disappearance of intracellular parasites led to resumed growth of the surviving organisms. The spleen cell factor(s) is effective when added either before or after exposure of the macrophages to trypomastigotes, and does not itself alter parasite viability. Dilution of the factor(s) up to 1:16 still results in significant trypanocidal activity. In vivo activated cells, obtained after a specific secondary challenge of animals infected with T. cruzi or Bacille Calmette-Guerin, lose their trypanocidal activity under in vitro conditions. This loss of activity can be prevented or restored by the addition of the active spleen cell factor(s). Induction of trypanocidal activity is also obtained with products from Concanavalin A- or lipopolysaccharide-stimulated normal spleen cells.

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Selected References

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  1. Anderson S. E., Bautista S., Remington J. S. Induction of resistance to Toxoplasma gondii in human macrophages by soluble lymphocyte products. J Immunol. 1976 Aug;117(2):381–387. [PubMed] [Google Scholar]
  2. Anderson S. E., Jr, Remington J. S. Effect of normal and activated human macrophages on Toxoplasma gondii. J Exp Med. 1974 May 1;139(5):1154–1174. doi: 10.1084/jem.139.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borges J. S., Johnson W. D., Jr Inhibition of multiplication of Toxoplasma gondii by human monocytes exposed to T-lymphocyte products. J Exp Med. 1975 Feb 1;141(2):483–496. doi: 10.1084/jem.141.2.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. COHN Z. A., BENSON B. THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. MORPHOLOGY, CYTOCHEMISTRY, AND BIOCHEMISTRY. J Exp Med. 1965 Jan 1;121:153–170. doi: 10.1084/jem.121.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fowles R. E., Fajardo I. M., Leibowitch J. L., David J. R. The enhancement of macrophage bacteriostasis by products of activated lymphocytes. J Exp Med. 1973 Oct 1;138(4):952–964. doi: 10.1084/jem.138.4.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Krahenbuhl J. L., Remington J. S. In vitro induction of nonspecific resistance in macrophages by specifically sensitized lymphocytes. Infect Immun. 1971 Oct;4(4):337–343. doi: 10.1128/iai.4.4.337-343.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lane F. C., Unanue E. R. Requirement of thymus (T) lymphocytes for resistance to listeriosis. J Exp Med. 1972 May 1;135(5):1104–1112. doi: 10.1084/jem.135.5.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. MACKANESS G. B. Cellular resistance to infection. J Exp Med. 1962 Sep 1;116:381–406. doi: 10.1084/jem.116.3.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. MACKANESS G. B. THE IMMUNOLOGICAL BASIS OF ACQUIRED CELLULAR RESISTANCE. J Exp Med. 1964 Jul 1;120:105–120. doi: 10.1084/jem.120.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mackaness G. B. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med. 1969 May 1;129(5):973–992. doi: 10.1084/jem.129.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mackaness G. B. The monocyte in cellular immunity. Semin Hematol. 1970 Apr;7(2):172–184. [PubMed] [Google Scholar]
  12. Munthe-Kaas A. C., Seglen P. O. The use of Metrizamide as a gradient medium for isopycnic separation of rat liver cells. FEBS Lett. 1974 Aug 1;43(3):252–256. doi: 10.1016/0014-5793(74)80654-x. [DOI] [PubMed] [Google Scholar]
  13. Nogueira N., Bianco C., Cohn Z. Studies on the selective lysis and purification of Trypanosoma cruzi. J Exp Med. 1975 Jul 1;142(1):224–229. doi: 10.1084/jem.142.1.224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nogueira N., Cohn Z. Trypanosoma cruzi: mechanism of entry and intracellular fate in mammalian cells. J Exp Med. 1976 Jun 1;143(6):1402–1420. doi: 10.1084/jem.143.6.1402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nogueira N., Gordon S., Cohn Z. Trypanosoma cruzi: modification of macrophage function during infection. J Exp Med. 1977 Jul 1;146(1):157–171. doi: 10.1084/jem.146.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nogueira N., Gordon S., Cohn Z. Trypanosoma cruzi: the immunological induction of macrophage plasminogen activator requires thymus-derived lymphocytes. J Exp Med. 1977 Jul 1;146(1):172–183. doi: 10.1084/jem.146.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. North R. J. Importance of thymus-derived lymphocytes in cell-mediated immunity to infection. Cell Immunol. 1973 Apr;7(1):166–176. doi: 10.1016/0008-8749(73)90193-7. [DOI] [PubMed] [Google Scholar]
  18. Ruco L. P., Meltzer M. S. Macrophage activation for tumor cytotoxicity: induction of tumoricidal macrophages by supernatants of PPD-stimulated Bacillus Calmette-Guérin-immune spleen cell cultures. J Immunol. 1977 Sep;119(3):889–896. [PubMed] [Google Scholar]
  19. Simon H. B., Sheagren J. N. Cellular immunity in vitro. I. Immunologically mediated enhancement of macrophage bactericidal capacity. J Exp Med. 1971 Jun 1;133(6):1377–1389. doi: 10.1084/jem.133.6.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Simon H. B., Sheagren J. N. Enhancement of macrophage bactericidal capacity by antigenically stimulated immune lymphocytes. Cell Immunol. 1972 Jun;4(2):163–174. doi: 10.1016/0008-8749(72)90015-9. [DOI] [PubMed] [Google Scholar]
  21. Williams D. M., Remington J. S. Effect of human monocytes and macrophages on Trypanosoma cruzi. Immunology. 1977 Jan;32(1):19–23. [PMC free article] [PubMed] [Google Scholar]

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