Passage of parasites across the blood-brain barrier

Willias Masocha 1, Krister Kristensson

Affiliations

01 March 2012

-

doi: 10.4161/viru.19178

Abstract

The blood-brain barrier (BBB) is a structural and functional barrier that protects the central nervous system (CNS) from invasion by blood-borne pathogens including parasites. However, some intracellular and extracellular parasites can traverse the BBB during the course of infection and cause neurological disturbances and/or damage which are at times fatal. The means by which parasites cross the BBB and how the immune system controls the parasites within the brain are still unclear. In this review we present the current understanding of the processes utilized by two human neuropathogenic parasites, Trypanosoma brucei spp and Toxoplasma gondii, to go across the BBB and consequences of CNS invasion. We also describe briefly other parasites that can invade the brain and how they interact with or circumvent the BBB. The roles played by parasite-derived and host-derived molecules during parasitic and white blood cell invasion of the brain are discussed.

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References

  1.  
    1. Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 2009;27:451–83. doi: 10.1146/annurev.immunol.021908.132532. - DOI - PubMed
  2.  
    1. Bencurova E, Mlynarcik P, Bhide M. An insight into the ligand-receptor interactions involved in the translocation of pathogens across blood-brain barrier. FEMS Immunol Med Microbiol. 2011;63:297–318. doi: 10.1111/j.1574-695X.2011.00867.x. - DOI - PubMed
  3.  
    1. Kim KS. Mechanisms of microbial traversal of the blood-brain barrier. Nat Rev Microbiol. 2008;6:625–34. doi: 10.1038/nrmicro1952. - DOI - PMC - PubMed
  4.  
    1. Kristensson K. Microbes’ roadmap to neurons. Nat Rev Neurosci. 2011;12:345–57. doi: 10.1038/nrn3029. - DOI - PubMed
  5.  
    1. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363:1965–76. doi: 10.1016/S0140-6736(04)16412-X. - DOI - PubMed
  6.  
    1. Dellacasa-Lindberg I, Hitziger N, Barragan A. Localized recrudescence of Toxoplasma infections in the central nervous system of immunocompromised mice assessed by in vivo bioluminescence imaging. Microbes Infect. 2007;9:1291–8. doi: 10.1016/j.micinf.2007.06.003. - DOI - PubMed
  7.  
    1. Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006;7:41–53. doi: 10.1038/nrn1824. - DOI - PubMed
  8.  
    1. Wilhelm I, Fazakas C, Krizbai IA. In vitro models of the blood-brain barrier. Acta Neurobiol Exp (Wars) 2011;71:113–28. - PubMed
  9.  
    1. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37:13–25. doi: 10.1016/j.nbd.2009.07.030. - DOI - PubMed
  10.  
    1. Armulik A, Genové G, Mäe M, Nisancioglu MH, Wallgard E, Niaudet C, et al. Pericytes regulate the blood-brain barrier. Nature. 2010;468:557–61. doi: 10.1038/nature09522. - DOI - PubMed
  11.  
    1. Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol. 2010;10:712–23. doi: 10.1038/nri2852. - DOI - PubMed
  12.  
    1. Engelhardt B, Sorokin L. The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol. 2009;31:497–511. doi: 10.1007/s00281-009-0177-0. - DOI - PubMed
  13.  
    1. Sixt M, Engelhardt B, Pausch F, Hallmann R, Wendler O, Sorokin LM. Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. J Cell Biol. 2001;153:933–46. doi: 10.1083/jcb.153.5.933. - DOI - PMC - PubMed
  14.  
    1. Owens T, Bechmann I, Engelhardt B. Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol. 2008;67:1113–21. doi: 10.1097/NEN.0b013e31818f9ca8. - DOI - PubMed
  15.  
    1. Broadwell RD, Sofroniew MV. Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. Exp Neurol. 1993;120:245–63. doi: 10.1006/exnr.1993.1059. - DOI - PubMed
  16.  
    1. Dowse TJ, Koussis K, Blackman MJ, Soldati-Favre D. Roles of proteases during invasion and egress by Plasmodium and Toxoplasma. Subcell Biochem. 2008;47:121–39. doi: 10.1007/978-0-387-78267-6_10. - DOI - PubMed
  17.  
    1. Dvorák J, Mashiyama ST, Braschi S, Sajid M, Knudsen GM, Hansell E, et al. Differential use of protease families for invasion by schistosome cercariae. Biochimie. 2008;90:345–58. doi: 10.1016/j.biochi.2007.08.013. - DOI - PubMed
  18.  
    1. He C, Nora GP, Schneider EL, Kerr ID, Hansell E, Hirata K, et al. A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target. J Biol Chem. 2010;285:18516–27. doi: 10.1074/jbc.M109.086181. - DOI - PMC - PubMed
  19.  
    1. Salter JP, Lim KC, Hansell E, Hsieh I, McKerrow JH. Schistosome invasion of human skin and degradation of dermal elastin are mediated by a single serine protease. J Biol Chem. 2000;275:38667–73. doi: 10.1074/jbc.M006997200. - DOI - PubMed
  20.  
    1. Barragan A, Sibley LD. Transepithelial migration of Toxoplasma gondii is linked to parasite motility and virulence. J Exp Med. 2002;195:1625–33. doi: 10.1084/jem.20020258. - DOI - PMC - PubMed
  21.  
    1. Barragan A, Brossier F, Sibley LD. Transepithelial migration of Toxoplasma gondii involves an interaction of intercellular adhesion molecule 1 (ICAM-1) with the parasite adhesin MIC2. Cell Microbiol. 2005;7:561–8. doi: 10.1111/j.1462-5822.2005.00486.x. - DOI - PubMed
  22.  
    1. Li H, Child MA, Bogyo M. Proteases as regulators of pathogenesis: Examples from the apicomplexa. Biochim Biophys Acta. 2012;1824:177–85. - PMC - PubMed
  23.  
    1. Däubener W, Spors B, Hucke C, Adam R, Stins M, Kim KS, et al. Restriction of Toxoplasma gondii growth in human brain microvascular endothelial cells by activation of indoleamine 2,3-dioxygenase. Infect Immun. 2001;69:6527–31. doi: 10.1128/IAI.69.10.6527-6531.2001. - DOI - PMC - PubMed
  24.  
    1. Lachenmaier SM, Deli MA, Meissner M, Liesenfeld O. Intracellular transport of Toxoplasma gondii through the blood-brain barrier. J Neuroimmunol. 2011;232:119–30. doi: 10.1016/j.jneuroim.2010.10.029. - DOI - PMC - PubMed
  25.  
    1. Taubert A, Krüll M, Zahner H, Hermosilla C. Toxoplasma gondii and Neospora caninum infections of bovine endothelial cells induce endothelial adhesion molecule gene transcription and subsequent PMN adhesion. Vet Immunol Immunopathol. 2006;112:272–83. doi: 10.1016/j.vetimm.2006.03.017. - DOI - PubMed
  26.  
    1. Unno A, Suzuki K, Xuan X, Nishikawa Y, Kitoh K, Takashima Y. Dissemination of extracellular and intracellular Toxoplasma gondii tachyzoites in the blood flow. Parasitol Int. 2008;57:515–8. doi: 10.1016/j.parint.2008.06.004. - DOI - PubMed
  27.  
    1. Bakalara N, Santarelli X, Davis C, Baltz T. Purification, cloning, and characterization of an acidic ectoprotein phosphatase differentially expressed in the infectious bloodstream form of Trypanosoma brucei. J Biol Chem. 2000;275:8863–71. doi: 10.1074/jbc.275.12.8863. - DOI - PubMed
  28.  
    1. Lonsdale-Eccles JD, Grab DJ. Trypanosome hydrolases and the blood-brain barrier. Trends Parasitol. 2002;18:17–9. doi: 10.1016/S1471-4922(01)02120-1. - DOI - PubMed
  29.  
    1. Grab DJ, Nikolskaia O, Kim YV, Lonsdale-Eccles JD, Ito S, Hara T, et al. African trypanosome interactions with an in vitro model of the human blood-brain barrier. J Parasitol. 2004;90:970–9. doi: 10.1645/GE-287R. - DOI - PubMed
  30.  
    1. de Sousa KP, Atouguia J, Silva MS. Partial biochemical characterization of a metalloproteinase from the bloodstream forms of Trypanosoma brucei brucei parasites. Protein J. 2010;29:283–9. doi: 10.1007/s10930-010-9250-8. - DOI - PubMed
  31.  
    1. Abdulla MH, O’Brien T, Mackey ZB, Sajid M, Grab DJ, McKerrow JH. RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model. PLoS Negl Trop Dis. 2008;2:e298. doi: 10.1371/journal.pntd.0000298. - DOI - PMC - PubMed
  32.  
    1. Nikolskaia OV, de A Lima AP, Kim YV, Lonsdale-Eccles JD, Fukuma T, Scharfstein J, et al. Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease. J Clin Invest. 2006;116:2739–47. - PMC - PubMed
  33.  
    1. Nikolskaia OV, Kim YV, Kovbasnjuk O, Kim KJ, Grab DJ. Entry of Trypanosoma brucei gambiense into microvascular endothelial cells of the human blood-brain barrier. Int J Parasitol. 2006;36:513–9. doi: 10.1016/j.ijpara.2006.01.011. - DOI - PubMed
  34.  
    1. Grab DJ, Garcia-Garcia JC, Nikolskaia OV, Kim YV, Brown A, Pardo CA, et al. Protease activated receptor signaling is required for African trypanosome traversal of human brain microvascular endothelial cells. PLoS Negl Trop Dis. 2009;3:e479. doi: 10.1371/journal.pntd.0000479. - DOI - PMC - PubMed
  35.  
    1. Grab DJ, Chakravorty SJ, van der Heyde H, Stins MF. How can microbial interactions with the blood-brain barrier modulate astroglial and neuronal function? Cell Microbiol. 2011;13:1470–8. doi: 10.1111/j.1462-5822.2011.01661.x. - DOI - PubMed
  36.  
    1. Ibrahim HM, Bannai H, Xuan X, Nishikawa Y. Toxoplasma gondii cyclophilin 18-mediated production of nitric oxide induces Bradyzoite conversion in a CCR5-dependent manner. Infect Immun. 2009;77:3686–95. doi: 10.1128/IAI.00361-09. - DOI - PMC - PubMed
  37.  
    1. Ibrahim HM, Xuan X, Nishikawa Y. Toxoplasma gondii cyclophilin 18 regulates the proliferation and migration of murine macrophages and spleen cells. Clin Vaccine Immunol. 2010;17:1322–9. doi: 10.1128/CVI.00128-10. - DOI - PMC - PubMed
  38.  
    1. Dellacasa-Lindberg I, Fuks JM, Arrighi RB, Lambert H, Wallin RP, Chambers BJ, et al. Migratory activation of primary cortical microglia upon infection with Toxoplasma gondii. Infect Immun. 2011;79:3046–52. doi: 10.1128/IAI.01042-10. - DOI - PMC - PubMed
  39.  
    1. Lambert H, Hitziger N, Dellacasa I, Svensson M, Barragan A. Induction of dendritic cell migration upon Toxoplasma gondii infection potentiates parasite dissemination. Cell Microbiol. 2006;8:1611–23. doi: 10.1111/j.1462-5822.2006.00735.x. - DOI - PubMed
  40.  
    1. Lambert H, Dellacasa-Lindberg I, Barragan A. Migratory responses of leukocytes infected with Toxoplasma gondii. Microbes Infect. 2011;13:96–102. doi: 10.1016/j.micinf.2010.10.002. - DOI - PubMed
  41.  
    1. Courret N, Darche S, Sonigo P, Milon G, Buzoni-Gâtel D, Tardieux I. CD11c- and CD11b-expressing mouse leukocytes transport single Toxoplasma gondii tachyzoites to the brain. Blood. 2006;107:309–16. doi: 10.1182/blood-2005-02-0666. - DOI - PMC - PubMed
  42.  
    1. Falangola MF, Petito CK. Choroid plexus infection in cerebral toxoplasmosis in AIDS patients. Neurology. 1993;43:2035–40. - PubMed
  43.  
    1. Deckert M, Lütjen S, Leuker CE, Kwok LY, Strack A, Müller W, et al. Mice with neonatally induced inactivation of the vascular cell adhesion molecule-1 fail to control the parasite in Toxoplasma encephalitis. Eur J Immunol. 2003;33:1418–28. doi: 10.1002/eji.200322826. - DOI - PubMed
  44.  
    1. Thomsen AR. Lymphocytic choriomeningitis virus-induced central nervous system disease: a model for studying the role of chemokines in regulating the acute antiviral CD8+ T-cell response in an immune-privileged organ. J Virol. 2009;83:20–8. doi: 10.1128/JVI.00682-08. - DOI - PMC - PubMed
  45.  
    1. Quan N, Mhlanga JD, Whiteside MB, McCoy AN, Kristensson K, Herkenham M. Chronic overexpression of proinflammatory cytokines and histopathology in the brains of rats infected with Trypanosoma brucei. J Comp Neurol. 1999;414:114–30. doi: 10.1002/(SICI)1096-9861(19991108)414:1<114::AID-CNE9>3.0.CO;2-G. - DOI - PubMed
  46.  
    1. Schultzberg M, Ambatsis M, Samuelsson EB, Kristensson K, van Meirvenne N. Spread of Trypanosoma brucei to the nervous system: early attack on circumventricular organs and sensory ganglia. J Neurosci Res. 1988;21:56–61. doi: 10.1002/jnr.490210109. - DOI - PubMed
  47.  
    1. Schwerk C, Rybarczyk K, Essmann F, Seibt A, Molleken ML, Zeni P, et al. TNFalpha induces choroid plexus epithelial cell barrier alterations by apoptotic and nonapoptotic mechanisms. J Biomed Biotechnol 2010; 2010:307231. - PMC - PubMed
  48.  
    1. Ngotho M, Kagira JM, Kariuki C, Maina N, Thuita JK, Mwangangi DM, et al. Influence of trypanocidal therapy on the haematology of vervet monkeys experimentally infected with Trypanosoma brucei rhodesiense. Acta Trop. 2011;119:14–8. doi: 10.1016/j.actatropica.2011.02.013. - DOI - PubMed
  49.  
    1. Rodgers J. Trypanosomiasis and the brain. Parasitology. 2010;137:1995–2006. doi: 10.1017/S0031182009991806. - DOI - PubMed
  50.  
    1. Feustel SM, Meissner M, Liesenfeld O. Toxoplasma gondii and the blood-brain barrier. Virulence. 2012;3:172–82. doi: 10.4161/viru.19004. - DOI - PMC - PubMed
  51.  
    1. Masocha W, Robertson B, Rottenberg ME, Mhlanga J, Sorokin L, Kristensson K. Cerebral vessel laminins and IFN-gamma define Trypanosoma brucei brucei penetration of the blood-brain barrier. J Clin Invest. 2004;114:689–94. - PMC - PubMed
  52.  
    1. Deckert-Schlüter M, Schlüter D, Hof H, Wiestler OD, Lassmann H. Differential expression of ICAM-1, VCAM-1 and their ligands LFA-1, Mac-1, CD43, VLA-4, and MHC class II antigens in murine Toxoplasma encephalitis: a light microscopic and ultrastructural immunohistochemical study. J Neuropathol Exp Neurol. 1994;53:457–68. doi: 10.1097/00005072-199409000-00005. - DOI - PubMed
  53.  
    1. Strack A, Asensio VC, Campbell IL, Schlüter D, Deckert M. Chemokines are differentially expressed by astrocytes, microglia and inflammatory leukocytes in Toxoplasma encephalitis and critically regulated by interferon-gamma. Acta Neuropathol. 2002;103:458–68. doi: 10.1007/s00401-001-0491-7. - DOI - PubMed
  54.  
    1. Silva NM, Manzan RM, Carneiro WP, Milanezi CM, Silva JS, Ferro EA, et al. Toxoplasma gondii: the severity of toxoplasmic encephalitis in C57BL/6 mice is associated with increased ALCAM and VCAM-1 expression in the central nervous system and higher blood-brain barrier permeability. Exp Parasitol. 2010;126:167–77. doi: 10.1016/j.exppara.2010.04.019. - DOI - PubMed
  55.  
    1. Wang X, Michie SA, Xu B, Suzuki Y. Importance of IFN-gamma-mediated expression of endothelial VCAM-1 on recruitment of CD8+ T cells into the brain during chronic infection with Toxoplasma gondii. J Interferon Cytokine Res. 2007;27:329–38. doi: 10.1089/jir.2006.0154. - DOI - PubMed
  56.  
    1. Masocha W, Amin DN, Kristensson K, Rottenberg ME. Differential invasion of Trypanosoma brucei brucei and lymphocytes into the brain of C57BL/6 and 129Sv/Ev mice. Scand J Immunol. 2008;68:484–91. doi: 10.1111/j.1365-3083.2008.02170.x. - DOI - PubMed
  57.  
    1. Amin DN, Vodnala SK, Masocha W, Sun B, Kristensson K, Rottenberg ME. Distinct Toll-like Receptor Signals Regulate Cerebral Parasite Load and Interferon alpha/beta and Tumor Necrosis Factor alpha-Dependent T-Cell Infiltration in the Brains of Trypanosoma brucei-Infected Mice. J Infect Dis. 2012;205:320–32. doi: 10.1093/infdis/jir734. - DOI - PMC - PubMed
  58.  
    1. Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989;59:1203–11. doi: 10.1016/0092-8674(89)90775-7. - DOI - PubMed
  59.  
    1. Bevilacqua MP, Stengelin S, Gimbrone MA, Jr., Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989;243:1160–5. doi: 10.1126/science.2466335. - DOI - PubMed
  60.  
    1. Hanemaaijer R, Koolwijk P, le Clercq L, de Vree WJ, van Hinsbergh VW. Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and phorbol ester. Biochem J. 1993;296:803–9. - PMC - PubMed
  61.  
    1. Zeni P, Doepker E, Schulze-Topphoff U, Huewel S, Tenenbaum T, Galla HJ. MMPs contribute to TNF-alpha-induced alteration of the blood-cerebrospinal fluid barrier in vitro. Am J Physiol Cell Physiol. 2007;293:C855–64. doi: 10.1152/ajpcell.00470.2006. - DOI - PubMed
  62.  
    1. Masocha W, Rottenberg ME, Kristensson K. Migration of African trypanosomes across the blood-brain barrier. Physiol Behav. 2007;92:110–4. doi: 10.1016/j.physbeh.2007.05.045. - DOI - PubMed
  63.  
    1. Amin DN, Rottenberg ME, Thomsen AR, Mumba D, Fenger C, Kristensson K, et al. Expression and role of CXCL10 during the encephalitic stage of experimental and clinical African trypanosomiasis. J Infect Dis. 2009;200:1556–65. doi: 10.1086/644597. - DOI - PubMed
  64.  
    1. Kristensson K, Nygård M, Bertini G, Bentivoglio M. African trypanosome infections of the nervous system: parasite entry and effects on sleep and synaptic functions. Prog Neurobiol. 2010;91:152–71. doi: 10.1016/j.pneurobio.2009.12.001. - DOI - PubMed
  65.  
    1. Maclean L, Odiit M, Macleod A, Morrison L, Sweeney L, Cooper A, et al. Spatially and genetically distinct African Trypanosome virulence variants defined by host interferon-gamma response. J Infect Dis. 2007;196:1620–8. doi: 10.1086/522011. - DOI - PMC - PubMed
  66.  
    1. Amin DN, Ngoyi DM, Nhkwachi GM, Palomba M, Rottenberg M, Büscher P, et al. Identification of stage biomarkers for human African trypanosomiasis. Am J Trop Med Hyg. 2010;82:983–90. doi: 10.4269/ajtmh.2010.09-0770. - DOI - PMC - PubMed
  67.  
    1. Hainard A, Tiberti N, Robin X, Lejon V, Ngoyi DM, Matovu E, et al. A combined CXCL10, CXCL8 and H-FABP panel for the staging of human African trypanosomiasis patients. PLoS Negl Trop Dis. 2009;3:e459. doi: 10.1371/journal.pntd.0000459. - DOI - PMC - PubMed
  68.  
    1. Hainard A, Tiberti N, Robin X, Ngoyi DM, Matovu E, Enyaru JC, et al. Matrix metalloproteinase-9 and intercellular adhesion molecule 1 are powerful staging markers for human African trypanosomiasis. Trop Med Int Health. 2011;16:119–26. doi: 10.1111/j.1365-3156.2010.02642.x. - DOI - PubMed
  69.  
    1. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–73. doi: 10.1146/annurev.iy.07.040189.001045. - DOI - PubMed
  70.  
    1. Paul WE, Seder RA. Lymphocyte responses and cytokines. Cell. 1994;76:241–51. doi: 10.1016/0092-8674(94)90332-8. - DOI - PubMed
  71.  
    1. Pearce EJ, MacDonald AS. The immunobiology of schistosomiasis. Nat Rev Immunol. 2002;2:499–511. doi: 10.1038/nri843. - DOI - PubMed
  72.  
    1. Mhlanga JD, Bentivoglio M, Kristensson K. Neurobiology of cerebral malaria and African sleeping sickness. Brain Res Bull. 1997;44:579–89. doi: 10.1016/S0361-9230(97)00309-2. - DOI - PubMed
  73.  
    1. Magez S, Stijlemans B, Baral T, De Baetselier P. VSG-GPI anchors of African trypanosomes: their role in macrophage activation and induction of infection-associated immunopathology. Microbes Infect. 2002;4:999–1006. doi: 10.1016/S1286-4579(02)01617-9. - DOI - PubMed
  74.  
    1. Hertz CJ, Filutowicz H, Mansfield JM. Resistance to the African trypanosomes is IFN-gamma dependent. J Immunol. 1998;161:6775–83. - PubMed
  75.  
    1. Lucas R, Magez S, Songa B, Darji A, Hamers R, de Baetselier P. A role for TNF during African trypanosomiasis: involvement in parasite control, immunosuppression and pathology. Res Immunol. 1993;144:370–6. doi: 10.1016/S0923-2494(93)80082-A. - DOI - PubMed
  76.  
    1. Schleifer KW, Filutowicz H, Schopf LR, Mansfield JM. Characterization of T helper cell responses to the trypanosome variant surface glycoprotein. J Immunol. 1993;150:2910–9. - PubMed
  77.  
    1. Rosenberg GA, Estrada EY, Dencoff JE, Stetler-Stevenson WG. Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic window. Brain Res. 1995;703:151–5. doi: 10.1016/0006-8993(95)01089-0. - DOI - PubMed
  78.  
    1. Gloor SM, Wachtel M, Bolliger MF, Ishihara H, Landmann R, Frei K. Molecular and cellular permeability control at the blood-brain barrier. Brain Res Brain Res Rev. 2001;36:258–64. doi: 10.1016/S0165-0173(01)00102-3. - DOI - PubMed
  79.  
    1. Yang GY, Gong C, Qin Z, Liu XH, Lorris Betz A. Tumor necrosis factor alpha expression produces increased blood-brain barrier permeability following temporary focal cerebral ischemia in mice. Brain Res Mol Brain Res. 1999;69:135–43. doi: 10.1016/S0169-328X(99)00007-8. - DOI - PubMed
  80.  
    1. Pereira-Chioccola VL, Vidal JE, Su C. Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients. Future Microbiol. 2009;4:1363–79. doi: 10.2217/fmb.09.89. - DOI - PubMed
  81.  
    1. Weiss LM, Dubey JP. Toxoplasmosis: A history of clinical observations. Int J Parasitol. 2009;39:895–901. doi: 10.1016/j.ijpara.2009.02.004. - DOI - PMC - PubMed
  82.  
    1. Suzuki Y, Sa Q, Gehman M, Ochiai E. Interferon-gamma- and perforin-mediated immune responses for resistance against Toxoplasma gondii in the brain. Expert Rev Mol Med. 2011;13:e31. doi: 10.1017/S1462399411002018. - DOI - PMC - PubMed
  83.  
    1. Yap G, Pesin M, Sher A. Cutting edge: IL-12 is required for the maintenance of IFN-gamma production in T cells mediating chronic resistance to the intracellular pathogen, Toxoplasma gondii. J Immunol. 2000;165:628–31. - PubMed
  84.  
    1. Gazzinelli RT, Wysocka M, Hayashi S, Denkers EY, Hieny S, Caspar P, et al. Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol. 1994;153:2533–43. - PubMed
  85.  
    1. Jones LA, Roberts F, Nickdel MB, Brombacher F, McKenzie AN, Henriquez FL, et al. IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii. Eur J Immunol. 2010;40:426–36. doi: 10.1002/eji.200939705. - DOI - PubMed
  86.  
    1. Pittella JE. Central nervous system involvement in Chagas disease: a hundred-year-old history. Trans R Soc Trop Med Hyg. 2009;103:973–8. doi: 10.1016/j.trstmh.2009.04.012. - DOI - PubMed
  87.  
    1. Rocha A, de Meneses AC, da Silva AM, Ferreira MS, Nishioka SA, Burgarelli MK, et al. Pathology of patients with Chagas’ disease and acquired immunodeficiency syndrome. Am J Trop Med Hyg. 1994;50:261–8. - PubMed
  88.  
    1. Da Silva AA, Pereira GV, de Souza AS, Silva RR, Rocha MS, Lannes-Vieira J. Trypanosoma cruzi-Induced Central Nervous System Alterations: From the Entry of Inflammatory Cells to Potential Cognitive and Psychiatric Abnormalities. J Neuroparasitol. 2010;1:101–13.
  89.  
    1. Combes V, El-Assaad F, Faille D, Jambou R, Hunt NH, Grau GE. Microvesiculation and cell interactions at the brain-endothelial interface in cerebral malaria pathogenesis. Prog Neurobiol. 2010;91:140–51. doi: 10.1016/j.pneurobio.2010.01.007. - DOI - PubMed
  90.  
    1. Hunt NH, Golenser J, Chan-Ling T, Parekh S, Rae C, Potter S, et al. Immunopathogenesis of cerebral malaria. Int J Parasitol. 2006;36:569–82. doi: 10.1016/j.ijpara.2006.02.016. - DOI - PubMed
  91.  
    1. Medana IM, Turner GD. Human cerebral malaria and the blood-brain barrier. Int J Parasitol. 2006;36:555–68. doi: 10.1016/j.ijpara.2006.02.004. - DOI - PubMed
  92.  
    1. Schmidt KE, Schumak B, Specht S, Dubben B, Limmer A, Hoerauf A. Induction of pro-inflammatory mediators in Plasmodium berghei infected BALB/c mice breaks blood-brain-barrier and leads to cerebral malaria in an IL-12 dependent manner. Microbes Infect. 2011;13:828–36. doi: 10.1016/j.micinf.2011.04.006. - DOI - PubMed
  93.  
    1. van der Heyde HC, Nolan J, Combes V, Gramaglia I, Grau GE. A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trends Parasitol. 2006;22:503–8. doi: 10.1016/j.pt.2006.09.002. - DOI - PubMed
  94.  
    1. Siddiqui R, Emes R, Elsheikha H, Khan NA. Area 51: How do Acanthamoeba invade the central nervous system? Trends Parasitol. 2011;27:185–9. doi: 10.1016/j.pt.2011.01.005. - DOI - PubMed
  95.  
    1. Matin A, Siddiqui R, Jayasekera S, Khan NA. Increasing importance of Balamuthia mandrillaris. Clin Microbiol Rev. 2008;21:435–48. doi: 10.1128/CMR.00056-07. - DOI - PMC - PubMed
  96.  
    1. Jayasekera S, Sissons J, Tucker J, Rogers C, Nolder D, Warhurst D, et al. Post-mortem culture of Balamuthia mandrillaris from the brain and cerebrospinal fluid of a case of granulomatous amoebic meningoencephalitis, using human brain microvascular endothelial cells. J Med Microbiol. 2004;53:1007–12. doi: 10.1099/jmm.0.45721-0. - DOI - PubMed
  97.  
    1. Matin A, Stins M, Kim KS, Khan NA. Balamuthia mandrillaris exhibits metalloprotease activities. FEMS Immunol Med Microbiol. 2006;47:83–91. doi: 10.1111/j.1574-695X.2006.00065.x. - DOI - PubMed
  98.  
    1. Siddiqui R, Khan NA. Balamuthia amoebic encephalitis: an emerging disease with fatal consequences. Microb Pathog. 2008;44:89–97. doi: 10.1016/j.micpath.2007.06.008. - DOI - PubMed
  99.  
    1. Matin A, Siddiqui R, Jung SY, Kim KS, Stins M, Khan NA. Balamuthia mandrillaris interactions with human brain microvascular endothelial cells in vitro. J Med Microbiol. 2007;56:1110–5. doi: 10.1099/jmm.0.47134-0. - DOI - PubMed
  100.  
    1. Rocha-Azevedo B, Jamerson M, Cabral GA, Silva-Filho FC, Marciano-Cabral F. The interaction between the amoeba Balamuthia mandrillaris and extracellular matrix glycoproteins in vitro. Parasitology. 2007;134:51–8. doi: 10.1017/S0031182006001272. - DOI - PubMed
  101.  
    1. Liao CW, Cho WL, Kao TC, Su KE, Lin YH, Fan CK. Blood-brain barrier impairment with enhanced SP, NK-1R, GFAP and claudin-5 expressions in experimental cerebral toxocariasis. Parasite Immunol. 2008;30:525–34. doi: 10.1111/j.1365-3024.2008.01048.x. - DOI - PubMed
  102.  
    1. Mahanty S, Garcia HH, Cysticercosis Working Group in Perú Cysticercosis and neurocysticercosis as pathogens affecting the nervous system. Prog Neurobiol. 2010;91:172–84. doi: 10.1016/j.pneurobio.2009.12.008. - DOI - PubMed
  103.  
    1. Prasad A, Prasad KN, Gupta RK, Pradhan S. Increased expression of ICAM-1 among symptomatic neurocysticercosis. J Neuroimmunol. 2009;206:118–20. doi: 10.1016/j.jneuroim.2008.09.015. - DOI - PubMed
  104.  
    1. Alvarez JI, Teale JM. Breakdown of the blood brain barrier and blood-cerebrospinal fluid barrier is associated with differential leukocyte migration in distinct compartments of the CNS during the course of murine NCC. J Neuroimmunol. 2006;173:45–55. doi: 10.1016/j.jneuroim.2005.11.020. - DOI - PubMed
  105.  
    1. Sikasunge CS, Johansen MV, Phiri IK, Willingham AL, 3rd, Leifsson PS. The immune response in Taenia solium neurocysticercosis in pigs is associated with astrogliosis, axonal degeneration and altered blood-brain barrier permeability. Vet Parasitol. 2009;160:242–50. doi: 10.1016/j.vetpar.2008.11.015. - DOI - PubMed
  106.  
    1. Schramm G, Haas H. Th2 immune response against Schistosoma mansoni infection. Microbes Infect. 2010;12:881–8. doi: 10.1016/j.micinf.2010.06.001. - DOI - PubMed
  107.  
    1. Ross AG, McManus DP, Farrar J, Hunstman RJ, Gray DJ, Li YS. Neuroschistosomiasis. J Neurol 2011. - PubMed
  108.  
    1. Ferrari TC, Moreira PR. Neuroschistosomiasis: clinical symptoms and pathogenesis. Lancet Neurol. 2011;10:853–64. doi: 10.1016/S1474-4422(11)70170-3. - DOI - PubMed
  109.  
    1. Pittella JE. Neuroschistosomiasis. Brain Pathol. 1997;7:649–62. doi: 10.1111/j.1750-3639.1997.tb01080.x. - DOI - PubMed
  110.  
    1. Heggie TW. Swimming with death: Naegleria fowleri infections in recreational waters. Travel Med Infect Dis. 2010;8:201–6. doi: 10.1016/j.tmaid.2010.06.001. - DOI - PubMed
  111.  
    1. Shin HJ, Cho MS, Jung SU, Kim HI, Park S, Kim HJ, et al. Molecular cloning and characterization of a gene encoding a 13.1 kDa antigenic protein of Naegleria fowleri. J Eukaryot Microbiol. 2001;48:713–7. doi: 10.1111/j.1550-7408.2001.tb00211.x. - DOI - PubMed
  112.  
    1. Cho MS, Jung SY, Park S, Kim KH, Kim HI, Sohn S, et al. Immunological characterizations of a cloned 13.1-kilodalton protein from pathogenic Naegleria fowleri. Clin Diagn Lab Immunol. 2003;10:954–9. - PMC - PubMed
  113.  
    1. Martinez AJ, Visvesvara GS. Free-living, amphizoic and opportunistic amebas. Brain Pathol. 1997;7:583–98. doi: 10.1111/j.1750-3639.1997.tb01076.x. - DOI - PubMed
  114.  
    1. Serrano-Luna J, Cervantes-Sandoval I, Tsutsumi V, Shibayama M. A biochemical comparison of proteases from pathogenic naegleria fowleri and non-pathogenic Naegleria gruberi. J Eukaryot Microbiol. 2007;54:411–7. doi: 10.1111/j.1550-7408.2007.00280.x. - DOI - PubMed
  115.  
    1. Idro R, Marsh K, John CC, Newton CR. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res. 2010;68:267–74. doi: 10.1203/PDR.0b013e3181eee738. - DOI - PMC - PubMed
  116.  
    1. Gulinello M, Acquarone M, Kim JH, Spray DC, Barbosa HS, Sellers R, et al. Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology. Microbes Infect. 2010;12:528–37. doi: 10.1016/j.micinf.2010.03.009. - DOI - PMC - PubMed
  117.  
    1. Lamberton PH, Donnelly CA, Webster JP. Specificity of the Toxoplasma gondii-altered behaviour to definitive versus non-definitive host predation risk. Parasitology. 2008;135:1143–50. doi: 10.1017/S0031182008004666. - DOI - PubMed
  118.  
    1. Jennings FW, Gray GD. Relapsed parasitaemia following chemotherapy of chronic T. brucei infections in mice and its relation to cerebral trypanosomes. Contrib Microbiol Immunol. 1983;7:147–54. - PubMed
  119.  
    1. Jennings FW, Whitelaw DD, Holmes PH, Chizyuka HG, Urquhart GM. The brain as a source of relapsing Trypanosoma brucei infection in mice after chemotherapy. Int J Parasitol. 1979;9:381–4. doi: 10.1016/0020-7519(79)90089-4. - DOI - PubMed
  120.  
    1. Moulton JE. Relapse infection after chemotherapy in goats experimentally infected with Trypanosoma brucei: pathological changes in central nervous system. Vet Pathol. 1986;23:21–8. - PubMed
  121.  
    1. Poltera AA, Sayer PD, Brighouse G, Bovell D, Rudin W. Immunopathological aspects of trypanosomal meningoencephalitis in vervet monkeys after relapse following Berenil treatment. Trans R Soc Trop Med Hyg. 1985;79:527–31. doi: 10.1016/0035-9203(85)90086-0. - DOI - PubMed
  122.  
    1. Ghumra A, Khunrae P, Ataide R, Raza A, Rogerson SJ, Higgins MK, et al. Immunisation with recombinant PfEMP1 domains elicits functional rosette-inhibiting and phagocytosis-inducing antibodies to Plasmodium falciparum. PLoS One. 2011;6:e16414. doi: 10.1371/journal.pone.0016414. - DOI - PMC - PubMed
  123.  
    1. Hviid L. The role of Plasmodium falciparum variant surface antigens in protective immunity and vaccine development. Hum Vaccin. 2010;6:84–9. doi: 10.4161/hv.6.1.9602. - DOI - PubMed
  124.  
    1. Rosenberg C, De Craeye S, Jongert E, Gargano N, Beghetto E, Del Porto P, et al. Induction of partial protection against infection with Toxoplasma gondii genotype II by DNA vaccination with recombinant chimeric tachyzoite antigens. Vaccine. 2009;27:2489–98. doi: 10.1016/j.vaccine.2009.02.058. - DOI - PubMed
  125.  
    1. Fernandez-Reyes D, Craig AG, Kyes SA, Peshu N, Snow RW, Berendt AR, et al. A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum Mol Genet. 1997;6:1357–60. doi: 10.1093/hmg/6.8.1357. - DOI - PubMed
  126.  
    1. McCormick CJ, Craig A, Roberts D, Newbold CI, Berendt AR. Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells. J Clin Invest. 1997;100:2521–9. doi: 10.1172/JCI119794. - DOI - PMC - PubMed
  127.  
    1. Newbold CI, Craig AG, Kyes S, Berendt AR, Snow RW, Peshu N, et al. PfEMP1, polymorphism and pathogenesis. Ann Trop Med Parasitol. 1997;91:551–7. doi: 10.1080/00034989760923. - DOI - PubMed
  128.  
    1. Oleinikov AV, Amos E, Frye IT, Rossnagle E, Mutabingwa TK, Fried M, et al. High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies. PLoS Pathog. 2009;5:e1000386. doi: 10.1371/journal.ppat.1000386. - DOI - PMC - PubMed
  129.  
    1. Smith JD, Craig AG, Kriek N, Hudson-Taylor D, Kyes S, Fagan T, et al. Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proc Natl Acad Sci U S A. 2000;97:1766–71. doi: 10.1073/pnas.040545897. - DOI - PMC - PubMed
  130.  
    1. Alsam S, Kim KS, Stins M, Rivas AO, Sissons J, Khan NA. Acanthamoeba interactions with human brain microvascular endothelial cells. Microb Pathog. 2003;35:235–41. doi: 10.1016/j.micpath.2003.07.001. - DOI - PubMed
  131.  
    1. Khan NA, Siddiqui R. Acanthamoeba affects the integrity of human brain microvascular endothelial cells and degrades the tight junction proteins. Int J Parasitol. 2009;39:1611–6. doi: 10.1016/j.ijpara.2009.06.004. - DOI - PubMed
  132.  
    1. Matin A, Jeong SR, Stins M, Khan NA. Effects of human serum on Balamuthia mandrillaris interactions with human brain microvascular endothelial cells. J Med Microbiol. 2007;56:30–5. doi: 10.1099/jmm.0.46847-0. - DOI - PubMed
  133.  
    1. Matin A, Khan NA. Demonstration and partial characterization of ecto-ATPase in Balamuthia mandrillaris and its possible role in the host-cell interactions. Lett Appl Microbiol. 2008;47:348–54. doi: 10.1111/j.1472-765X.2008.02414.x. - DOI - PubMed
  134.  
    1. Othman AA, Abdel-Aleem GA, Saied EM, Mayah WW, Elatrash AM. Biochemical and immunopathological changes in experimental neurotoxocariasis. Mol Biochem Parasitol. 2010;172:1–8. doi: 10.1016/j.molbiopara.2010.03.006. - DOI - PubMed

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