Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1988 Apr;56(4):849–854. doi: 10.1128/iai.56.4.849-854.1988

Cerebrospinal fluid macrophage response to experimental cryptococcal meningitis: relationship between in vivo and in vitro measurements of cytotoxicity.

J R Perfect 1, M M Hobbs 1, D L Granger 1, D T Durack 1
PMCID: PMC259380  PMID: 3346075

Abstract

The functional abilities of macrophages from cerebrospinal fluid (CSF) have so far been little studied. We examined the acquisition of activation characteristics by CSF macrophages during the course of experimental cryptococcal meningitis. CSF macrophages developed the ability for increased reactive oxidative intermediate (H2O2) production and tumor and fungal cytotoxicity. Despite having been activated, CSF macrophages could not inhibit the growth of Cryptococcus neoformans in vitro. Immunosuppression with cyclosporine, which eliminates the natural resistance of rabbits to cryptococcal meningitis, did not prevent or diminish H2O2 production by CSF macrophages but did reduce their tumoricidal activity. Activation of CSF macrophages appears to be an integral part of the central nervous system immune response to C. neoformans in this model, but alone is insufficient to eliminate C. neoformans from the central nervous system.

Full text

PDF
854

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alberti S., Boraschi D., Luini W., Tagliabue A. Effects of in vivo treatments with cyclosporin-A on mouse cell-mediated immune responses. Int J Immunopharmacol. 1981;3(4):357–364. doi: 10.1016/0192-0561(81)90031-x. [DOI] [PubMed] [Google Scholar]
  2. Biggar W. D., Buron S., Holmes B. Bactericidal mechanisms in rabbit alveolar macrophages: evidence against peroxidase and hydrogen peroxide bactericidal mechanisms. Infect Immun. 1976 Jul;14(1):6–10. doi: 10.1128/iai.14.1.6-10.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Black C. M., Beaman B. L., Donovan R. M., Goldstein E. Effect of virulent and less virulent strains of Nocardia asteroides on acid-phosphatase activity in alveolar and peritoneal macrophages maintained in vitro. J Infect Dis. 1983 Jul;148(1):117–124. doi: 10.1093/infdis/148.1.117. [DOI] [PubMed] [Google Scholar]
  4. Bunjes D., Hardt C., Röllinghoff M., Wagner H. Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2. Eur J Immunol. 1981 Aug;11(8):657–661. doi: 10.1002/eji.1830110812. [DOI] [PubMed] [Google Scholar]
  5. Catterall J. R., Black C. M., Leventhal J. P., Rizk N. W., Wachtel J. S., Remington J. S. Nonoxidative microbicidal activity in normal human alveolar and peritoneal macrophages. Infect Immun. 1987 Jul;55(7):1635–1640. doi: 10.1128/iai.55.7.1635-1640.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collins F. M., Niederbuhl C. J., Campbell S. G. Bactericidal activity of alveolar and peritoneal macrophages exposed in vitro to three strains of Pasteurella multocida. Infect Immun. 1983 Feb;39(2):779–784. doi: 10.1128/iai.39.2.779-784.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Curiel T. J., Perfect J. R., Durack D. T. Leukocyte subpopulations in cerebrospinal fluid of normal rabbits. Lab Anim Sci. 1982 Dec;32(6):622–624. [PubMed] [Google Scholar]
  8. Diamond R. D., Bennett J. E. Growth of Cryptococcus neoformans within human macrophages in vitro. Infect Immun. 1973 Feb;7(2):231–236. doi: 10.1128/iai.7.2.231-236.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drath D. B., Kahan B. D. Alterations in rat pulmonary macrophage function by the immunosuppressive agents cyclosporine, azathioprine, and prednisolone. Transplantation. 1983 Jun;35(6):588–592. doi: 10.1097/00007890-198306000-00014. [DOI] [PubMed] [Google Scholar]
  10. Ganz T., Selsted M. E., Szklarek D., Harwig S. S., Daher K., Bainton D. F., Lehrer R. I. Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest. 1985 Oct;76(4):1427–1435. doi: 10.1172/JCI112120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Granger D. L., Perfect J. R., Durack D. T. Macrophage-mediated fungistasis: requirement for a macromolecular component in serum. J Immunol. 1986 Jul 15;137(2):693–701. [PubMed] [Google Scholar]
  12. Granger D. L., Perfect J. R., Durack D. T. Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide. J Clin Invest. 1985 Aug;76(2):508–516. doi: 10.1172/JCI112000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guseo A. Classification of cells in the cerebrospinal fluid. A review. Eur Neurol. 1977;15(3):169–176. doi: 10.1159/000114808. [DOI] [PubMed] [Google Scholar]
  14. Hibbs J. B., Jr, Taintor R. R., Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science. 1987 Jan 23;235(4787):473–476. doi: 10.1126/science.2432665. [DOI] [PubMed] [Google Scholar]
  15. KONIGSMARK B. W., SIDMAN R. L. ORIGIN OF BRAIN MACROPHAGES IN THE MOUSE. J Neuropathol Exp Neurol. 1963 Oct;22:643–676. doi: 10.1097/00005072-196310000-00006. [DOI] [PubMed] [Google Scholar]
  16. Kitz D. J., Johnson C. R., Kobayashi G. S., Medoff G., Little J. R. Growth inhibition of Cryptococcus neoformans by cloned cultured murine macrophages. Cell Immunol. 1984 Oct 15;88(2):489–500. doi: 10.1016/0008-8749(84)90180-1. [DOI] [PubMed] [Google Scholar]
  17. Lehrer R. I., Ferrari L. G., Patterson-Delafield J., Sorrell T. Fungicidal activity of rabbit alveolar and peritoneal macrophages against Candida albicans. Infect Immun. 1980 Jun;28(3):1001–1008. doi: 10.1128/iai.28.3.1001-1008.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lehrer R. I. The fungicidal mechanisms of human monocytes. I. Evidence for myeloperoxidase-linked and myeloperoxidase-independent candidacidal mechanisms. J Clin Invest. 1975 Feb;55(2):338–346. doi: 10.1172/JCI107937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lepay D. A., Steinman R. M., Nathan C. F., Murray H. W., Cohn Z. A. Liver macrophages in murine listeriosis. Cell-mediated immunity is correlated with an influx of macrophages capable of generating reactive oxygen intermediates. J Exp Med. 1985 Jun 1;161(6):1503–1512. doi: 10.1084/jem.161.6.1503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lisak R. P., Zweiman B. In vitro cell-mediated immunity of cerebrospinal-fluid lymphocytes to myelin basic protein in primary demyelinating diseases. N Engl J Med. 1977 Oct 20;297(16):850–853. doi: 10.1056/NEJM197710202971602. [DOI] [PubMed] [Google Scholar]
  21. McCabe R. E., Remington J. S., Araujo F. G. In vivo and in vitro effects of cyclosporin A on Trypanosoma cruzi. Am J Trop Med Hyg. 1985 Sep;34(5):861–865. doi: 10.4269/ajtmh.1985.34.861. [DOI] [PubMed] [Google Scholar]
  22. McKeever P. E., Balentine J. D. Macrophages migration through the brain parenchyma to the perivascular space following particle ingestion. Am J Pathol. 1978 Oct;93(1):153–164. [PMC free article] [PubMed] [Google Scholar]
  23. Mitchell T. G., Friedman L. In vitro phagocytosis and intracellular fate of variously encapsulated strains of Cryptococcus neoformans. Infect Immun. 1972 Apr;5(4):491–498. doi: 10.1128/iai.5.4.491-498.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Murray H. W., Juangbhanich C. W., Nathan C. F., Cohn Z. A. Macrophage oxygen-dependent antimicrobial activity. II. The role of oxygen intermediates. J Exp Med. 1979 Oct 1;150(4):950–964. doi: 10.1084/jem.150.4.950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nathan C., Nogueira N., Juangbhanich C., Ellis J., Cohn Z. Activation of macrophages in vivo and in vitro. Correlation between hydrogen peroxide release and killing of Trypanosoma cruzi. J Exp Med. 1979 May 1;149(5):1056–1068. doi: 10.1084/jem.149.5.1056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. North R. J. The concept of the activated macrophage. J Immunol. 1978 Sep;121(3):806–809. [PMC free article] [PubMed] [Google Scholar]
  27. Oehmichen M. Are resting and/or reactive microglia macrophages? Immunobiology. 1982 Apr;161(3-4):246–254. doi: 10.1016/S0171-2985(82)80080-6. [DOI] [PubMed] [Google Scholar]
  28. Patterson-Delafield J., Martinez R. J., Lehrer R. I. Microbicidal cationic proteins in rabbit alveolar macrophages: a potential host defense mechanism. Infect Immun. 1980 Oct;30(1):180–192. doi: 10.1128/iai.30.1.180-192.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Perfect J. R., Durack D. T. Effects of cyclosporine in experimental cryptococcal meningitis. Infect Immun. 1985 Oct;50(1):22–26. doi: 10.1128/iai.50.1.22-26.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Perfect J. R., Granger D. L., Durack D. T. Effects of antifungal agents and gamma interferon on macrophage cytotoxicity for fungi and tumor cells. J Infect Dis. 1987 Aug;156(2):316–323. doi: 10.1093/infdis/156.2.316. [DOI] [PubMed] [Google Scholar]
  31. Perfect J. R., Lang S. D., Durack D. T. Chronic cryptococcal meningitis: a new experimental model in rabbits. Am J Pathol. 1980 Oct;101(1):177–194. [PMC free article] [PubMed] [Google Scholar]
  32. Pick E., Mizel D. Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods. 1981;46(2):211–226. doi: 10.1016/0022-1759(81)90138-1. [DOI] [PubMed] [Google Scholar]
  33. Prineas J. W., Wright R. G. Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab Invest. 1978 Apr;38(4):409–421. [PubMed] [Google Scholar]
  34. Roessmann U., Friede R. L. Entry of labeled monocytic cells into the central nervous system. Acta Neuropathol. 1968 Jun 7;10(4):359–362. doi: 10.1007/BF00690711. [DOI] [PubMed] [Google Scholar]
  35. Sasada M., Johnston R. B., Jr Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages. J Exp Med. 1980 Jul 1;152(1):85–98. doi: 10.1084/jem.152.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schaffner A., Douglas H., Braude A. I., Davis C. E. Killing of Aspergillus spores depends on the anatomical source of the macrophage. Infect Immun. 1983 Dec;42(3):1109–1115. doi: 10.1128/iai.42.3.1109-1115.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Selsted M. E., Szklarek D., Ganz T., Lehrer R. I. Activity of rabbit leukocyte peptides against Candida albicans. Infect Immun. 1985 Jul;49(1):202–206. doi: 10.1128/iai.49.1.202-206.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Takashima T., Collins F. M. Immunosuppressive effect of cyclosporin A on Mycobacterium bovis BCG infections in mice. Infect Immun. 1987 Jul;55(7):1701–1706. doi: 10.1128/iai.55.7.1701-1706.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Thomson A. W., Moon D. K., Geczy C. L., Nelson D. S. Cyclosporin A inhibits lymphokine production but not the responses of macrophages to lymphokines. Immunology. 1983 Feb;48(2):291–299. [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES