Abstract
The term “severe malaria” refers to a wide spectrum of syndromes in Plasmodium-infected humans including cerebral malaria (CM), respiratory distress, severe anemia, liver dysfunction, and hypoglycemia. Mouse models have been employed to further our understanding of the pathology and immune responses that occur during Plasmodium infection. Evidence of brain, liver, lung, and spleen pathology, as well as anemia and tissue-sequestration of parasites, has been reported in various strains of inbred mice. While no single mouse model mimics all the various clinical manifestations of severe malaria in humans, here we describe a detailed protocol for Plasmodium berghei ANKA infection of C57BL/6J mice. For many years, this model has been referred to as “experimental cerebral malaria,” but in fact recapitulates many of the symptoms and pathologies observed in most severe malaria syndromes.
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References
Engwerda CE, Belnoue E, Gruner AC, Renia L (2005) Experimental models of cerebral malaria. Curr Top Microbiol Immunol 297:103–143
Stevenson MM, Riley EM (2004) Innate immunity to malaria. Nat Rev Immunol 4(3):169–180
Taylor-Robinson AW (2010) Regulation of immunity to Plasmodium: implications from mouse models for blood stage malaria vaccine design. Exp Parasitol 126(3):406–414
Langhorne J, Quin SJ, Sanni LA (2002) Mouse models of blood-stage malaria infections: immune responses and cytokines involved in protection and pathology. Chem Immunol 80(80):204–228
Brian de Souza J, Hafalla JC, Riley EM, Couper KN (2010) Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease. Parasitology 137(05):755–772
Hall N, Karras M, Raine JD et al (2005) A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science 307(5706):82–86
van Dijk MR, Waters AP, Janse CJ (1995) Stable transfection of malaria parasite blood stages. Science 268(5215):1358–1362
Tomas AM, van der Wel AM, Thomas AW, Janse CJ, Waters AP (1998) Transfection systems for animal models of malaria. Parasitol Today 14(6):245–249
Stevenson MM, Gros P, Olivier M, Fortin A, Serghides L (2010) Cerebral malaria: human versus mouse studies. Trends Parasitol 26(6):274–275
Amante FH, Haque A, Stanley AC et al (2010) Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. J Immunol 185(6):3632–3642
Baptista FG, Pamplona A, Pena AC, Mota MM, Pied S, Vigario AM (2010) Accumulation of Plasmodium berghei-infected red blood cells in the brain is crucial for the development of cerebral malaria in mice. Infect Immun 78(9):4033–4039
Schofield L, Grau GE (2005) Immunological processes in malaria pathogenesis. Nat Rev Immunol 5(9):722–735
Reis PA, Comim CM, Hermani F et al (2010) Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy. PLoS Pathog 6(6):e1000963
Desruisseaux MS, Gulinello M, Smith DN et al (2008) Cognitive dysfunction in mice infected with Plasmodium berghei strain ANKA. J Infect Dis 197(11):1621–1627
Thumwood CM, Hunt NH, Cowden WB, Clark IA (1988) Breakdown of the blood-brain barrier in murine cerebral malaria. Parasitology 96(03):579–589
Etienne-Manneville S, Manneville JB, Adamson P, Wilbourn B, Greenwood J, Couraud PO (2000) ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines. J Immunol 165(6):3375–3383
Haque A, Best SE, Unosson K et al (2011) Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria. J Immunol 186(11):6148–6156
Nitcheu J, Bonduelle O, Combadiere C et al (2003) Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis. J Immunol 170(4):2221–2228
Potter S, Chan-Ling T, Ball HJ et al (2006) Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. Int J Parasitol 36(4):485–496
Belnoue E, Kayibanda M, Vigario AM et al (2002) On the pathogenic role of brain-sequestered αβ CD8+ T cells in experimental cerebral malaria. J Immunol 169(11):6369–6375
Lovegrove FE, Gharib SA, Pena-Castillo L et al (2008) Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model. PLoS Pathog 4(5):e1000068
Epiphanio S, Campos MG, Pamplona A et al (2010) VEGF promotes malaria-associated acute lung injury in mice. PLoS Pathog 6(5):e1000916
Helegbe G, Yanagi T, Senba M et al (2011) Histopathological studies in two strains of semi-immune mice infected with Plasmodium berghei ANKA after chronic exposure. Parasitol Res 108(4):807–814
Chang W-L, Jones SP, Lefer DJ et al (2001) CD8 + -T-cell depletion ameliorates circulatory shock in Plasmodium berghei-infected mice. Infect Immun 69(12):7341–7348
Weerasinghe K, Galappaththy G, Fernando WP et al (2002) A safety and efficacy trial of artesunate, sulphadoxine-pyrimethamine and primaquine in P falciparum malaria. Ceylon Med J 47(3):83
Haque A, Best SE, Amante FH et al (2011) High parasite burdens cause liver damage in mice following Plasmodium berghei ANKA infection independently of CD8+ T cell-mediated immune pathology. Infect Immun 79(5):1882–1888
Berendt AR, Tumer GDH, Newbold CI (1994) Cerebral malaria: the sequestration hypothesis. Parasitol Today 10(10):412–414
MacPherson G, Warrell MJ, White NJ, Looareesuwan S, Warrell DA (1985) Human cerebral malaria. A quantitative ultrastructural analysis of parasitised erythrocyte sequestration. Am J Pathol 119:385–401
Dondorp AM, Desakorn V, Pongtavornpinyo W et al (2005) Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med 2(8):e204
Fonager J, Pasini EM, Braks JA et al (2012) Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo. J Exp Med 209(1):93–107
Nie CQ, Bernard NJ, Schofield L, Hansen DS (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(5):2275–2282
Villegas-Mendez A, de Souza JB, Murungi L et al (2011) Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-γ during Plasmodium berghei ANKA infection. J Immunol 187(6):2885–2897
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de Oca, M.M., Engwerda, C., Haque, A. (2013). Plasmodium berghei ANKA (PbA) Infection of C57BL/6J Mice: A Model of Severe Malaria. In: Allen, I. (eds) Mouse Models of Innate Immunity. Methods in Molecular Biology, vol 1031. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-481-4_23
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DOI: https://doi.org/10.1007/978-1-62703-481-4_23
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