This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hearn, J.
Right arrow Articles by de Souza, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hearn, J.
Right arrow Articles by de Souza, J. B.

 Previous Article  |  Next Article 

Infection and Immunity, September 2000, p. 5364-5376, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Immunopathology of Cerebral Malaria: Morphological Evidence of Parasite Sequestration in Murine Brain Microvasculature

Jocelyn Hearn,1 Neil Rayment,1 David N. Landon,2 David R. Katz,1 and J. Brian de Souza1,*

Department of Immunology, Royal Free and University College London Medical School, Windeyer Institute of Medical Science, London W1P 6DB,1 and Department of Neuropathology, Institute of Neurology, London WC1N 3BG,2 United Kingdom

Received 13 March 2000/Returned for modification 12 May 2000/Accepted 10 June 2000

A murine model that closely resembles human cerebral malaria is presented, in which characteristic features of parasite sequestration and inflammation in the brain are clearly demonstrable. "Young" (BALB/c × C57BL/6)F1 mice infected with Plasmodium berghei (ANKA) developed typical neurological symptoms 7 to 8 days later and then died, although their parasitemias were below 20%. Older animals were less susceptible. Immunohistopathology and ultrastructure demonstrated that neurological symptoms were associated with sequestration of both parasitized erythrocytes and leukocytes and with clogging and rupture of vessels in both cerebral and cerebellar regions. Increases in tumor necrosis factor alpha and CD54 expression were also present. Similar phenomena were absent or substantially reduced in older infected but asymptomatic animals. These findings suggest that this murine model is suitable both for determining precise pathogenetic features of the cerebral form of the disease and for evaluating circumventive interventions.


* Corresponding author. Mailing address: Department of Immunology, Royal Free and University College London Medical School, Windeyer Institute of Medical Science, 46 Cleveland Street, London W1P 6DB, United Kingdom. Phone: 44-020 7679 9354. Fax: 44-020 7679 9357. E-mail: J.deSouza{at}ucl.ac.uk.


Infection and Immunity, September 2000, p. 5364-5376, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Cserti, C. M., Dzik, W. H. (2007). The ABO blood group system and Plasmodium falciparum malaria. Blood 110: 2250-2258 [Abstract] [Full Text]  
  • Lepenies, B., Pfeffer, K., Hurchla, M. A., Murphy, T. L., Murphy, K. M., Oetzel, J., Fleischer, B., Jacobs, T. (2007). Ligation of B and T Lymphocyte Attenuator Prevents the Genesis of Experimental Cerebral Malaria. J. Immunol. 179: 4093-4100 [Abstract] [Full Text]  
  • Vigario, A. M., Belnoue, E., Gruner, A. C., Mauduit, M., Kayibanda, M., Deschemin, J.-C., Marussig, M., Snounou, G., Mazier, D., Gresser, I., Renia, L. (2007). Recombinant Human IFN-{alpha} Inhibits Cerebral Malaria and Reduces Parasite Burden in Mice. J. Immunol. 178: 6416-6425 [Abstract] [Full Text]  
  • Nie, C. Q., Bernard, N. J., Schofield, L., Hansen, D. S. (2007). CD4+ CD25+ Regulatory T Cells Suppress CD4+ T-Cell Function and Inhibit the Development of Plasmodium berghei-Specific TH1 Responses Involved in Cerebral Malaria Pathogenesis. Infect. Immun. 75: 2275-2282 [Abstract] [Full Text]  
  • Hansen, D. S., Bernard, N. J., Nie, C. Q., Schofield, L. (2007). NK Cells Stimulate Recruitment of CXCR3+ T Cells to the Brain during Plasmodium berghei-Mediated Cerebral Malaria. J. Immunol. 178: 5779-5788 [Abstract] [Full Text]  
  • Gramaglia, I., Sahlin, H., Nolan, J. P., Frangos, J. A., Intaglietta, M., van der Heyde, H. C. (2005). Cell- Rather Than Antibody-Mediated Immunity Leads to the Development of Profound Thrombocytopenia during Experimental Plasmodium berghei Malaria. J. Immunol. 175: 7699-7707 [Abstract] [Full Text]  
  • Penet, M.-F., Viola, A., Confort-Gouny, S., Le Fur, Y., Duhamel, G., Kober, F., Ibarrola, D., Izquierdo, M., Coltel, N., Gharib, B., Grau, G. E., Cozzone, P. J. (2005). Imaging Experimental Cerebral Malaria In Vivo: Significant Role of Ischemic Brain Edema. J. Neurosci. 25: 7352-7358 [Abstract] [Full Text]  
  • Franke-Fayard, B., Janse, C. J., Cunha-Rodrigues, M., Ramesar, J., Buscher, P., Que, I., Lowik, C., Voshol, P. J., den Boer, M. A. M., van Duinen, S. G., Febbraio, M., Mota, M. M., Waters, A. P. (2005). From The Cover: Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proc. Natl. Acad. Sci. USA 102: 11468-11473 [Abstract] [Full Text]  
  • Voza, T., Vigario, A. M., Belnoue, E., Gruner, A. C., Deschemin, J.-C., Kayibanda, M., Delmas, F., Janse, C. J., Franke-Fayard, B., Waters, A. P., Landau, I., Snounou, G., Renia, L. (2005). Species-Specific Inhibition of Cerebral Malaria in Mice Coinfected with Plasmodium spp.. Infect. Immun. 73: 4777-4786 [Abstract] [Full Text]  
  • Combes, V., Rosenkranz, A. R., Redard, M., Pizzolato, G., Lepidi, H., Vestweber, D., Mayadas, T. N., Grau, G. E. (2004). Pathogenic Role of P-Selectin in Experimental Cerebral Malaria: Importance of the Endothelial Compartment. Am. J. Pathol. 164: 781-786 [Abstract] [Full Text]  
  • Sun, G., Chang, W.-L., Li, J., Berney, S. M., Kimpel, D., van der Heyde, H. C. (2003). Inhibition of Platelet Adherence to Brain Microvasculature Protects against Severe Plasmodium berghei Malaria. Infect. Immun. 71: 6553-6561 [Abstract] [Full Text]  
  • OZWARA, H., LANGERMANS, J. A. M., MAAMUN, J., FARAH, I. O., YOLE, D. S., MWENDA, J. M., WEILER, H., THOMAS, A. W. (2003). EXPERIMENTAL INFECTION OF THE OLIVE BABOON (PAPIO ANUBIS) WITH PLASMODIUM KNOWLESI: SEVERE DISEASE ACCOMPANIED BY CEREBRAL INVOLVEMENT. Am J Trop Med Hyg 69: 188-194 [Abstract] [Full Text]  
  • Belnoue, E., Costa, F. T. M., Vigario, A. M., Voza, T., Gonnet, F., Landau, I., van Rooijen, N., Mack, M., Kuziel, W. A., Renia, L. (2003). Chemokine Receptor CCR2 Is Not Essential for the Development of Experimental Cerebral Malaria. Infect. Immun. 71: 3648-3651 [Abstract] [Full Text]  
  • Belnoue, E., Kayibanda, M., Deschemin, J.-C., Viguier, M., Mack, M., Kuziel, W. A., Renia, L. (2003). CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood 101: 4253-4259 [Abstract] [Full Text]  
  • Hanum P., S., Hayano, M., Kojima, S. (2003). Cytokine and chemokine responses in a cerebral malaria-susceptible or -resistant strain of mice to Plasmodium berghei ANKA infection: early chemokine expression in the brain. Int Immunol 15: 633-640 [Abstract] [Full Text]  
  • Chang, W.-L., Li, J., Sun, G., Chen, H.-L., Specian, R. D., Berney, S. M., Granger, D. N., van der Heyde, H. C. (2003). P-Selectin Contributes to Severe Experimental Malaria but Is Not Required for Leukocyte Adhesion to Brain Microvasculature. Infect. Immun. 71: 1911-1918 [Abstract] [Full Text]  
  • Belnoue, E., Kayibanda, M., Vigario, A. M., Deschemin, J.-C., Rooijen, N. v., Viguier, M., Snounou, G., Renia, L. (2002). On the Pathogenic Role of Brain-Sequestered {alpha}{beta} CD8+ T Cells in Experimental Cerebral Malaria. J. Immunol. 169: 6369-6375 [Abstract] [Full Text]  
  • de Souza, J. B., Todd, J., Krishegowda, G., Gowda, D. C., Kwiatkowski, D., Riley, E. M. (2002). Prevalence and Boosting of Antibodies to Plasmodium falciparum Glycosylphosphatidylinositols and Evaluation of Their Association with Protection from Mild and Severe Clinical Malaria. Infect. Immun. 70: 5045-5051 [Abstract] [Full Text]  
  • Engwerda, C. R., Mynott, T. L., Sawhney, S., De Souza, J. B., Bickle, Q. D., Kaye, P. M. (2002). Locally Up-regulated Lymphotoxin {alpha}, Not Systemic Tumor Necrosis Factor {alpha}, Is the Principle Mediator of Murine Cerebral Malaria. JEM 195: 1371-1377 [Abstract] [Full Text]  
  • Bagot, S., Idrissa Boubou, M., Campino, S., Behrschmidt, C., Gorgette, O., Guenet, J.-L., Penha-Goncalves, C., Mazier, D., Pied, S., Cazenave, P.-A. (2002). Susceptibility to Experimental Cerebral Malaria Induced by Plasmodium berghei ANKA in Inbred Mouse Strains Recently Derived from Wild Stock. Infect. Immun. 70: 2049-2056 [Abstract] [Full Text]  
  • Chang, W.-L., Jones, S. P., Lefer, D. J., Welbourne, T., Sun, G., Yin, L., Suzuki, H., Huang, J., Granger, D. N., van der Heyde, H. C. (2001). CD8+-T-Cell Depletion Ameliorates Circulatory Shock in Plasmodium berghei-Infected Mice. Infect. Immun. 69: 7341-7348 [Abstract] [Full Text]  
  • Lou, J., Lucas, R., Grau, G. E. (2001). Pathogenesis of Cerebral Malaria: Recent Experimental Data and Possible Applications for Humans. Clin. Microbiol. Rev. 14: 810-820 [Abstract] [Full Text]  
  • Piguet, P. F., Da Kan, C., Vesin, C., Rochat, A., Donati, Y., Barazzone, C. (2001). Role of CD40-CD40L in Mouse Severe Malaria. Am. J. Pathol. 159: 733-742 [Abstract] [Full Text]