Abstract
The immunopathology of Trypanosoma brucei brucei in the central nervous system was studied by using an experimental model of chronic meningoencephalitis in outbred CD-1 mice. Mice infected with T. b. brucei were treated with a subcurative dose of the trypanocidal compound diaminazine aceturate. These mice relapsed and were again drug treated. The brains were examined histologically and by immunocytochemistry to identify activated astrocytes. The polymerase chain reaction was used to detect cytokine RNA transcripts. The infected and treated animals developed severe chronic meningoencephalitis characterized by large numbers of inflammatory cells and widespread astrocyte proliferation. In uninfected controls, only interleukin 1 and beta-actin RNA transcripts were detected while transcripts for beta-actin, tumor necrosis factor alpha, macrophage inflammatory protein 1 and interleukins 1 and 4 were demonstrated in the brains of infected animals. Gamma interferon and interleukin 6 were also detected in a few of the infected animals, but interleukin 2 was not found in any of these animals.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams J. H., Haller L., Boa F. Y., Doua F., Dago A., Konian K. Human African trypanosomiasis (T.b. gambiense): a study of 16 fatal cases of sleeping sickness with some observations on acute reactive arsenical encephalopathy. Neuropathol Appl Neurobiol. 1986 Jan-Feb;12(1):81–94. doi: 10.1111/j.1365-2990.1986.tb00682.x. [DOI] [PubMed] [Google Scholar]
- Anthoons J. A., Van Marck E. A., Gigase P. L., Stevens W. J. Immunohistochemical characterization of the mononuclear cells in the brain of the rat with an experimental chronic Trypanosoma brucei gambiense infection. Parasitol Res. 1989;75(4):251–256. doi: 10.1007/BF00931808. [DOI] [PubMed] [Google Scholar]
- Askonas B. A., Bancroft G. J. Interaction of African trypanosomes with the immune system. Philos Trans R Soc Lond B Biol Sci. 1984 Nov 13;307(1131):41–49. doi: 10.1098/rstb.1984.0107. [DOI] [PubMed] [Google Scholar]
- Bancroft G. J., Sutton C. J., Morris A. G., Askonas B. A. Production of interferons during experimental African trypanosomiasis. Clin Exp Immunol. 1983 Apr;52(1):135–143. [PMC free article] [PubMed] [Google Scholar]
- Bocci V. Central nervous system toxicity of interferons and other cytokines. J Biol Regul Homeost Agents. 1988 Jul-Sep;2(3):107–118. [PubMed] [Google Scholar]
- Bowlin T. L., Bitonti A. J., McKown B. J. Decreased interleukin-2 responsiveness in leukocytes from Trypanosoma brucei-infected mice. Cell Immunol. 1988 Apr 1;112(2):437–441. doi: 10.1016/0008-8749(88)90313-9. [DOI] [PubMed] [Google Scholar]
- Brenner C. A., Tam A. W., Nelson P. A., Engleman E. G., Suzuki N., Fry K. E., Larrick J. W. Message amplification phenotyping (MAPPing): a technique to simultaneously measure multiple mRNAs from small numbers of cells. Biotechniques. 1989 Nov-Dec;7(10):1096–1103. [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Eng L. F. Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol. 1985 Jun;8(4-6):203–214. doi: 10.1016/s0165-5728(85)80063-1. [DOI] [PubMed] [Google Scholar]
- Fontana A., Hengartner H., de Tribolet N., Weber E. Glioblastoma cells release interleukin 1 and factors inhibiting interleukin 2-mediated effects. J Immunol. 1984 Apr;132(4):1837–1844. [PubMed] [Google Scholar]
- Frei K., Malipiero U. V., Leist T. P., Zinkernagel R. M., Schwab M. E., Fontana A. On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases. Eur J Immunol. 1989 Apr;19(4):689–694. doi: 10.1002/eji.1830190418. [DOI] [PubMed] [Google Scholar]
- Gijbels K., Van Damme J., Proost P., Put W., Carton H., Billiau A. Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis. Eur J Immunol. 1990 Jan;20(1):233–235. doi: 10.1002/eji.1830200134. [DOI] [PubMed] [Google Scholar]
- Jennings F. W., Gray G. D. Relapsed parasitaemia following chemotherapy of chronic T. brucei infections in mice and its relation to cerebral trypanosomes. Contrib Microbiol Immunol. 1983;7:147–154. [PubMed] [Google Scholar]
- Jennings F. W., McNeil P. E., Ndung'u J. M., Murray M. Trypanosomiasis and encephalitis: possible aetiology and treatment. Trans R Soc Trop Med Hyg. 1989 Jul-Aug;83(4):518–519. doi: 10.1016/0035-9203(89)90272-1. [DOI] [PubMed] [Google Scholar]
- Krueger J. M., Walter J., Dinarello C. A., Wolff S. M., Chedid L. Sleep-promoting effects of endogenous pyrogen (interleukin-1). Am J Physiol. 1984 Jun;246(6 Pt 2):R994–R999. doi: 10.1152/ajpregu.1984.246.6.R994. [DOI] [PubMed] [Google Scholar]
- Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
- Lieberman A. P., Pitha P. M., Shin H. S., Shin M. L. Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6348–6352. doi: 10.1073/pnas.86.16.6348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mantovani A., Dejana E. Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today. 1989 Nov;10(11):370–375. doi: 10.1016/0167-5699(89)90270-3. [DOI] [PubMed] [Google Scholar]
- Mizel S. B. The interleukins. FASEB J. 1989 Oct;3(12):2379–2388. doi: 10.1096/fasebj.3.12.2676681. [DOI] [PubMed] [Google Scholar]
- Nawroth P. P., Bank I., Handley D., Cassimeris J., Chess L., Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1363–1375. doi: 10.1084/jem.163.6.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pentreath V. W. Neurobiology of sleeping sickness. Parasitol Today. 1989 Jul;5(7):215–218. doi: 10.1016/0169-4758(89)90273-1. [DOI] [PubMed] [Google Scholar]
- Pentreath V. W., Rees K., Owolabi O. A., Philip K. A., Doua F. The somnogenic T lymphocyte suppressor prostaglandin D2 is selectively elevated in cerebrospinal fluid of advanced sleeping sickness patients. Trans R Soc Trop Med Hyg. 1990 Nov-Dec;84(6):795–799. doi: 10.1016/0035-9203(90)90085-s. [DOI] [PubMed] [Google Scholar]
- Poltera A. A. Pathology of human African trypanosomiasis with reference to experimental African trypanosomiasis and infections of the central nervous system. Br Med Bull. 1985 Apr;41(2):169–174. doi: 10.1093/oxfordjournals.bmb.a072045. [DOI] [PubMed] [Google Scholar]
- Ramilo O., Sáez-Llorens X., Mertsola J., Jafari H., Olsen K. D., Hansen E. J., Yoshinaga M., Ohkawara S., Nariuchi H., McCracken G. H., Jr Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. J Exp Med. 1990 Aug 1;172(2):497–507. doi: 10.1084/jem.172.2.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robbins D. S., Shirazi Y., Drysdale B. E., Lieberman A., Shin H. S., Shin M. L. Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes. J Immunol. 1987 Oct 15;139(8):2593–2597. [PubMed] [Google Scholar]
- Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
- Saukkonen K., Sande S., Cioffe C., Wolpe S., Sherry B., Cerami A., Tuomanen E. The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. J Exp Med. 1990 Feb 1;171(2):439–448. doi: 10.1084/jem.171.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmidt H., Bafort J. M. African trypanosomiasis: treatment-induced invasion of brain and encephalitis. Am J Trop Med Hyg. 1985 Jan;34(1):64–68. doi: 10.4269/ajtmh.1985.34.64. [DOI] [PubMed] [Google Scholar]
- Schultzberg M., Olsson T., Samuelsson E. B., Maehlen J., Kristensson K. Early major histocompatibility complex (MHC) class I antigen induction in hypothalamic supraoptic and paraventricular nuclei in trypanosome-infected rats. J Neuroimmunol. 1989 Sep;24(1-2):105–112. doi: 10.1016/0165-5728(89)90104-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sileghem M., Hamers R., De Baetselier P. Experimental Trypanosoma brucei infections selectively suppress both interleukin 2 production and interleukin 2 receptor expression. Eur J Immunol. 1987 Oct;17(10):1417–1421. doi: 10.1002/eji.1830171005. [DOI] [PubMed] [Google Scholar]
- Veeken H. J., Ebeling M. C., Dolmans W. M. Trypanosomiasis in a rural hospital in Tanzania. A retrospective study of its management and the results of treatment. Trop Geogr Med. 1989 Apr;41(2):113–117. [PubMed] [Google Scholar]
- Waage A., Halstensen A., Shalaby R., Brandtzaeg P., Kierulf P., Espevik T. Local production of tumor necrosis factor alpha, interleukin 1, and interleukin 6 in meningococcal meningitis. Relation to the inflammatory response. J Exp Med. 1989 Dec 1;170(6):1859–1867. doi: 10.1084/jem.170.6.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolpe S. D., Davatelis G., Sherry B., Beutler B., Hesse D. G., Nguyen H. T., Moldawer L. L., Nathan C. F., Lowry S. F., Cerami A. Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties. J Exp Med. 1988 Feb 1;167(2):570–581. doi: 10.1084/jem.167.2.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong G. H., Bartlett P. F., Clark-Lewis I., McKimm-Breschkin J. L., Schrader J. W. Interferon-gamma induces the expression of H-2 and Ia antigens on brain cells. J Neuroimmunol. 1985 Feb-Mar;7(5-6):255–278. doi: 10.1016/s0165-5728(84)80026-0. [DOI] [PubMed] [Google Scholar]