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Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA

Published online by Cambridge University Press:  24 August 2016

YAN DING ,
WENYUE XU ,
TAOLI ZHOU ,
TAIPING LIU ,
HONG ZHENG  and
YONG FU
YAN DING
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
WENYUE XU
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
TAOLI ZHOU
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
TAIPING LIU
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
HONG ZHENG
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
YONG FU*
Affiliation:
Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China
*
*Corresponding author: Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China. E-mail: [email protected]
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Summary

Malaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM.

Keywords

cerebral malariamurine modelpathogenesisimmune responsePlasmodium berghei ANKAKM mice
Type
Research Article
Information
Parasitology , Volume 143 , Issue 12 , October 2016 , pp. 1672 - 1680
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Copyright
Copyright © Cambridge University Press 2016 

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References

REFERENCES

Adams, S., Brown, H. and Turner, G. (2002). Breaking down the blood-brain barrier: signaling a path to cerebral malaria? Trends in Parasitology 18, 360–366.Google Scholar
Amani, V., Boubou, M. I., Pied, S., Marussig, M., Walliker, D., Mazier, D. and Rénia, L. (1998). Cloned lines of Plasmodium berghei ANKA differ in their abilities to induce experimental cerebral malaria. Infection and Immunity 66, 4093–4099.Google Scholar
Amante, F. H., Stanley, A. C., Randall, L. M., Zhou, Y., Haque, A., McSweeney, K., Waters, A. P., Janse, C. J., Good, M. F., Hill, G. R. and Engwerda, C. R. (2007). A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. American Journal of Pathology 171, 548–559.Google Scholar
Amante, F. H., Haque, A., Stanley, A. C., Rivera Fde, L., Randall, L. M., Wilson, Y. A., Yeo, G., Pieper, C., Crabb, B. S., de Koning-Ward, T. F., Lundie, R. J., Good, M. F., Pinzon-Charry, A., Pearson, M. S., Duke, M. G., McManus, D. P., Loukas, A., Hill, G. R. and Engwerda, C. R. (2010). Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. Journal of Immunology 185, 3632–3642.Google Scholar
Bagot, S., Campino, S., Penha-Goncalves, C., Pied, S., Cazenave, P. A. and Holmberg, D. (2002). Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain. Proceedings of the National Academy of Sciences of the United States of America 99, 9919–9923.Google Scholar
Bagot, S., Nogueira, F., Collette, A., do Rosario, V., Lemonier, F., Cazenave, P. A. and Pied, S. (2004). Comparative study of brain CD8+ T cells induced by sporozoites and those induced by blood-stage Plasmodium berghei ANKA involved in the development of cerebral malaria. Infection and Immunity 72, 2817–2826.Google Scholar
Belnoue, E., Kayibanda, M. L., Vigario, A. M., Deschemin, J.-C., Rooijen, N. V., Viguier, M., Snounou, G. and Rénia, L. (2002). On the pathogenic role of brain-sequestered αβ CD8+ T cells in experimental cerebral Malaria. Journal of Immunology 169, 6369–6375.Google Scholar
Belnoue, E., Potter, S. M., Rosa, D. S., Mauduit, M., Gruner, A. C., Kayibanda, M., Mitchell, A. J., Hunt, N. H. and Renia, L. (2008). Control of pathogenic CD8+ T cell migration to the brain by IFN-gamma during experimental cerebral malaria. Parasite Immunology 30, 544–553.Google Scholar
Berkley, J. A., Mwangi, I., Mellington, F., Mwarumba, S. and Marsh, K. (1999). Cerebral malaria versus bacterial meningitis in children with impaired consciousness. QJM: Monthly Journal of the Association of Physicians 92, 151–157.Google Scholar
Breman, J. G. (2001). The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. American Journal of Tropical Medicine and Hygiene 64, 1–11.Google Scholar
Campanella, G. S., Tager, A. M., El Khoury, J. K., Thomas, S. Y., Abrazinski, T. A., Manice, L. A., Colvin, R. A. and Luster, A. D. (2008). Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proceedings of the National Academy of Sciences of the United States of America 105, 4814–4819.CrossRefGoogle ScholarPubMed
Chia, R., Achilli, F., Festing, M. F. and Fisher, E. M. (2005). The origins and uses of mouse outbred stocks. Nature Genetics 37, 1181–1186.CrossRefGoogle ScholarPubMed
Claser, C., Malleret, B., Gun, S. Y., Wong, A. Y., Chang, Z. W., Teo, P., See, P. C., Howland, S. W., Ginhoux, F. and Renia, L. (2011). CD8+ T cells and IFN-gamma mediate the time-dependent accumulation of infected red blood cells in deep organs during experimental cerebral malaria. PLoS ONE 6, e18720.Google Scholar
de Souza, J. B., Hafalla, J. C., Riley, E. M. and Couper, K. N. (2010). Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease. Parasitology 137, 755–772.Google Scholar
de Walick, S., Amante, F. H., McSweeney, K. A., Randall, L. M., Stanley, A. C., Haque, A., Kuns, R. D., MacDonald, K. P., Hill, G. R. and Engwerda, C. R. (2007). Cutting edge: conventional dendritic cells are the critical APC required for the induction of experimental cerebral malaria. Journal of Immunology 178, 6033–6037.Google Scholar
Engwerda, C. (2005). Experimental models of cerebral Malaria. Current Topics in Microbiology and Immunology 297, 103–143.Google Scholar
Engwerda, C. R., Mynott, T. L., Sawhney, S., De Souza, J. B., Bickle, Q. D. and Kaye, P. M. (2002). Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria. Journal of Experimental Medicine 195, 1371–1377.Google Scholar
Fonseca, L., Seixas, E., Butcher, G. and Langhorne, J. (2007). Cytokine responses of CD4+ T cells during a Plasmodium chabaudi chabaudi (ER) blood-stage infection in mice initiated by the natural route of infection. Malaria Journal 6, 77.CrossRefGoogle ScholarPubMed
Franke-Fayard, B., Waters, A. P. and Janse, C. J. (2006). Real-time in vivo imaging of transgenic bioluminescent blood stages of rodent malaria parasites in mice. Nature Protocols 1, 476–485.CrossRefGoogle ScholarPubMed
Gysin, J., Aikawa, M., Tourneur, N. and Tegoshi, T. (1992). Experimental Plasmodium falciparum cerebral malaria in the squirrel monkey Saimiri sciureus. Experimental Parasitology 75, 390–398.Google Scholar
Haldar, K., Murphy, S. C., Milner, D. A. and Taylor, T. E. (2007). Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease. Annual Review of Pathology 2, 217–249.Google Scholar
Hansen, D. S., Bernard, N. J., Nie, C. Q. and Schofield, L. (2007). NK cells stimulate recruitment of CXCR3+ T cells to the brain during Plasmodium berghei-mediated cerebral malaria. Journal of Immunology 178, 5779–5788.Google Scholar
Haque, A., Best, S. E., Unosson, K., Amante, F. H., de Labastida, F., Anstey, N. M., Karupiah, G., Smyth, M. J., Heath, W. R. and Engwerda, C. R. (2011). Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria. Journal of Immunology 186, 6148–6156.Google Scholar
Ibiwoye, M. O., Howard, C. V., Sibbons, P., Hasan, M. and van Velzen, D. (1993). Cerebral malaria in the rhesus monkey (Macaca mulatta): observations on host pathology. Journal of Comparative Pathology 108, 303–310.Google Scholar
Idro, R., Jenkins, N. E. and Newton, C. R. (2005). Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurology 4, 827–840.Google Scholar
Idro, R., Kakooza-Mwesige, A., Balyejjussa, S., Mirembe, G., Mugasha, C., Tugumisirize, J. and Byarugaba, J. (2010 a). Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children. BMC Research Notes 3, 104.Google Scholar
Idro, R., Marsh, K., John, C. C. and Newton, C. R. (2010 b). Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatric Research 68, 267–274.Google Scholar
Jambou, R., Combes, V., Jambou, M. J., Weksler, B. B., Couraud, P. O. and Grau, G. E. (2010). Plasmodium falciparum adhesion on human brain microvascular endothelial cells involves transmigration-like cup formation and induces opening of intercellular junctions. PLoS Pathogens 6, e1001021.Google Scholar
Khan, Z. M., Ng, C. and Vanderberg, J. P. (1992). Early hepatic stages of Plasmodium berghei: release of circumsporozoite protein and host cellular inflammatory response. Infection and Immunity 60, 264–270.Google Scholar
Lovegrove, F. E., Pena-Castillo, L., Mohammad, N., Liles, W. C., Hughes, T. R. and Kain, K. C. (2006). Simultaneous host and parasite expression profiling identifies tissue-specific transcriptional programs associated with susceptibility or resistance to experimental cerebral malaria. BMC Genomics 7, 295.Google Scholar
Lundie, R. J., de Koning-Ward, T. F., Davey, G. M., Nie, C. Q., Hansen, D. S., Lau, L. S., Mintern, J. D., Belz, G. T., Schofield, L., Carbone, F. R., Villadangos, J. A., Crabb, B. S. and Heath, W. R. (2008). Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8α + dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 105, 14509–14514.CrossRefGoogle ScholarPubMed
Martins, Y. C., Smith, M. J., Pelajo-Machado, M., Werneck, G. L., Lenzi, H. L., Daniel-Ribeiro, C. T. and Carvalho, L. J. (2009). Characterization of cerebral malaria in the outbred Swiss Webster mouse infected by Plasmodium berghei ANKA. International Journal of Experimental Pathology 90, 119–130.CrossRefGoogle ScholarPubMed
McQuillan, J. A., Mitchell, A. J., Ho, Y. F., Combes, V., Ball, H. J., Golenser, J., Grau, G. E. and Hunt, N. H. (2011). Coincident parasite and CD8 T cell sequestration is required for development of experimental cerebral malaria. International Journal for Parasitology 41, 155–163.Google Scholar
Miu, J., Mitchell, A. J., Muller, M., Carter, S. L., Manders, P. M., McQuillan, J. A., Saunders, B. M., Ball, H. J., Lu, B., Campbell, L. L. and Hunt, N. H. (2008). Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. Journal of Immunology 180, 1217–1230.Google Scholar
Muntendam, A. H., Jaffar, S., Bleichrodt, N. and van Hensbroek, M. B. (1996). Absence of neuropsychological sequelae following cerebral malaria in Gambian children. Transactions of the Royal Society of Tropical Medicine and Hygiene 90, 391–394.CrossRefGoogle ScholarPubMed
Murray, C. J., Rosenfeld, L. C., Lim, S. S., Andrews, K. G., Foreman, K. J., Haring, D., Fullman, N., Naghavi, M., Lozano, R. and Lopez, A. D. (2012). Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet 379, 413–431.Google Scholar
Nitcheu, J., Bonduelle, O., Combadiere, C., Tefit, M., Seilhean, D., Mazier, D. and Combadiere, B. (2003). Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis. Journal of Immunology 170, 2221–2228.Google Scholar
Renia, L., Potter, S. M., Mauduit, M., Rosa, D. S., Kayibanda, M., Deschemin, J. C., Snounou, G. and Gruner, A. C. (2006). Pathogenic T cells in cerebral malaria. International Journal for Parasitology 36, 547–554.Google Scholar
Shang, H., Wei, H., Yue, B., Xu, P. and Huang, H. (2009). Microsatellite analysis in two populations of Kunming mice. Laboratory Animals 43, 34–40.Google Scholar
van der Heyde, H. C., Bauer, P., Sun, G., Chang, W. L., Yin, L., Fuseler, J. and Granger, D. N. (2001). Assessing vascular permeability during experimental cerebral malaria by a radiolabeled monoclonal antibody technique. Infection and Immunity 69, 3460–3465.Google Scholar
Villegas-Mendez, A., de Souza, J. B., Murungi, L., Hafalla, J. C., Shaw, T. N., Greig, R., Riley, E. M. and Couper, K. N. (2011). Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection. Journal of Immunology 187, 2885–2897.Google Scholar
Warrell, D. A., Molyneux, M. E. and Beales, P. F. (1990). Severe and complicated malaria. World Health Organization, division of control of tropical diseases. Transactions of the Royal Society of Tropical Medicine and Hygiene 84 (Suppl. 2), 1–65.Google Scholar
WHO (2014). World malaria report 2014. World Health Organization.Google Scholar
Yalcin, B., Willis-Owen, S. A., Fullerton, J., Meesaq, A., Deacon, R. M., Rawlins, J. N., Copley, R. R., Morris, A. P., Flint, J. and Mott, R. (2004). Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice. Nature Genetics 36, 1197–1202.Google Scholar