Cerebral malaria: Gamma-interferon redux

Frontiers in Cellular and Infection Microbiology

Volumn 4, Issue AUG, 2014, Pages

  Hunt, Nicholas H ^a   Ball, Helen J ^a   Hansen, Anna M ^a   Khaw, Loke T ^a,b   Guo, Jintao ^a   Bakmiwewa, Supun ^a   Mitchell, Andrew J ^a   Combes, Valéry ^a   Grau, Georges E R ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b UNIVERSITY OF MALAYA   (Malaysia)

Author keywords

Blood brain barrier; Cerebral malaria; Immunopathology; Interferon gamma; Kynurenine pathway; Microparticles; Platelets

Indexed keywords

CD36 ANTIGEN; CD40 ANTIGEN; CHEMOKINE RECEPTOR CXCR3; CXCL9 CHEMOKINE; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INDOLEAMINE DIOXYGENASE 1; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 10; KYNURENINE; LYMPHOTOXIN; OXYGENASE; QUINOLINIC ACID; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1;

BLOOD VESSEL OCCLUSION; BRAIN MALARIA; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DISEASE SEVERITY; GENE EXPRESSION; HUMAN; HYPOXIA; IMMUNE RESPONSE; NONHUMAN; REGULATORY T LYMPHOCYTE; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; DISEASE MODEL; ENDOTHELIUM CELL; GENETICS; MALARIA, CEREBRAL; METABOLISM;

ANIMALS; DISEASE MODELS, ANIMAL; ENDOTHELIAL CELLS; HUMANS; INTERFERON-GAMMA; MALARIA, CEREBRAL; SIGNAL TRANSDUCTION;

EID: 84925354479     PISSN: None     EISSN: 22352988     Source Type: Journal    
DOI: 10.3389/fcimb.2014.00113     Document Type: Review

References (142)

1. Adam, R., Russing, D., Adams, O., Ailyati, A., Sik Kim, K., Schroten, H., et al. (2005). Role of human brain microvascular endothelial cells during central nervous system infection. Significance of indoleamine 2,3-dioxygenase in antimicrobial defence and immunoregulation. Thromb. Haemost. 94, 341-346. doi: 10.1267/THRO05020341
2. Adams, S., Brown, H., Turner, G. (2002). Breaking down the blood-brain barrier: signaling a path to cerebral malaria? Trends Parasitol. 18, 360-366. doi: 10.1016/S1471-4922(02)02353-X
3. Amani, V., Vigario, A. M., Belnoue, E., Marussig, M., Fonseca, L., Mazier, D., et al. (2000). Involvement of IFN-gamma receptor-mediated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection. Eur. J. Immunol. 30, 1646-1655. doi: 10.1002/1521-4141(200006)30:61646::AIDIMMU1646 3.0.CO;2-0
4. Amante, F. H., Haque, A., Stanley, A. C., Rivera, F. D., Randall, L. M., Wilson, Y. A., et al. (2010). Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. J. Immunol. 185, 3632-3642. doi: 10.4049/jimmunol. 1000944
5. Amante, F. H., Stanley, A. C., Randall, L. M., Zhou, Y., Haque, A., McSweeney, K., et al. (2007). A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. Am. J. Pathol. 171, 548-559. doi: 10.2353/ajpath.2007.061033
6. Ampawong, S., Chaisri, U., Viriyavejakul, P., Nontprasert, A., Grau, G. E., Pongponratn, E. (2014). Electron microscopic features of brain edemain rodent cerebral malaria in relation to glial fibrillary acidic protein expression. Int. J. Clin. Exp. Pathol. 7, 2056-2067.
7. Armah, H. B., Wilson, N. O., Sarfo, B. Y., Powell, M. D., Bond, V. C., Anderson, W., et al. (2007). Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children. Malar. J. 6:147. doi: 10.1186/1475-2875-6-147
8. Armah, H., Dodoo, A. K., Wiredu, E. K., Stiles, J. K., Adjei, A. A., Gyasi, R. K., et al. (2005). High-level cerebellar expression of cytokines and adhesion molecules in fatal, paediatric, cerebral malaria. Ann. Trop. Med. Parasitol. 99, 629-647. doi: 10.1179/136485905X51508
9. Artavanis-Tsakonas, K., Riley, E. M. (2002). Innate immune response to malaria: rapid induction of IFN-gamma from human NK cells by live Plasmodium falciparum-infected erythrocytes. J. Immunol. 169, 2956-2963. doi: 10.4049/jimmunol.169.6.2956
10. Ball, E. A., Sambo, M. R., Martins, M., Trovoada, M. J., Benchimol, C., Costa, J., et al. (2013). IFNAR1 controls progression to cerebral malaria in children and CD8+T cell brain pathology in Plasmodium berghei-infected mice. J. Immunol. 190, 5118-5127. doi: 10.4049/jimmunol.1300114
11. Ball, H. J., Yuasa, H. J., Austin, C. J., Weiser, S., Hunt, N. H. (2009). Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway. Int. J. Biochem. CellBiol. 41, 467-471. doi: 10.1016/j.biocel.2008.01.005
12. Baratin, M., Roetynck, S., Lepolard, C., Falk, C., Sawadogo, S., Uematsu, S., et al. (2005). Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to Plasmodium falciparum. Proc. Natl. Acad. Sci. U.S.A. 102, 14747-14752. doi: 10.1073/pnas.0507355102
13. Bauer, P. R., Van Der Heyde, H. C., Sun, G., Specian, R. D., Granger, D. N. (2002). Regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria. Micro circulation 9, 463-470. doi: 10.1038/sj.mn.7800159
14. Beare, N. A., Southern, C., Chalira, C., Taylor, T. E., Molyneux, M. E., Harding, S. P. (2004). Prognostic significance and course of retinopathy in children with severe malaria. Arch. Ophthalmol. 122, 1141-1147. doi: 10.1001/archopht.122.8.1141
15. Belnoue, E., Kayibanda, M., Vigario, A. M., Deschemin, J. C., van Rooijen, N., Viguier, M., et al. (2002). On the pathogenic role of brain-sequestered alphabeta CD8+T cells in experimental cerebral malaria.J. Immunol. 169, 6369-6375. doi: 10.4049/jimmunol.169.11.6369
16. Belnoue, E., Potter, S. M., Rosa, D. S., Mauduit, M., Gruner, A. C., Kayibanda, M., et al. (2008). Control of pathogenic CD8+T cell migration to the brain by IFNgamma during experimental cerebral malaria. Parasite Immunol. 30, 544-553. doi: 10.1111/j.1365-3024.2008.01053.x
17. Berendt, A. R., Turner, G. D. H., Newbold, C. I. (1994). Cerebral malaria: the sequestration hypothesis. Parasitol. Today 10, 412-414. doi: 10.1016/0169- 4758(94)90238-0
18. Billiau, A., Matthys, P. (2009). Interferon-gamma: a historical perspective. Cytokine Growth Factor Rev. 20, 97-113. doi: 10.1016/j.cytogfr.2009.02.004
19. Birbeck, G. L., Beare, N., Lewallen, S., Glover, S. J., Molyneux, M. E., Kaplan, P. W., et al. (2010). Identification of malaria retinopathy improves the specificity of the clinical diagnosis of cerebral malaria: findings from a prospective cohort study. Am. J. Trop. Med. Hyg. 82, 231-234. doi: 10.4269/ajtmh.2010.09-0532
20. Brown, H., Hien, T. T., Day, N., Mai, N., Chuong, L. V., Chau, T. T., et al. (1999a). Evidence of blood-brain barrier dysfunction in human cerebral malaria. Neuropathol. Appl. Neurobiol. 25, 331-340. doi: 10.1046/j.1365- 2990.1999.00188.x
21. Brown, H., Rogerson, S., Taylor, T., Tembo, M., Mwenechanya, J., Molyneux, M., et al. (2001). Blood-brain barrier function in cerebral malaria in Malawian children. Am. J. Trop. Med. Hyg. 64, 207-213.
22. Brown, H., Turner, G., Rogerson, S., Tembo, M., Mwenechanya, J., Molyneux, M., et al. (1999b). Cytokine expression in the brain in human cerebral malaria. J. Infect. Dis. 180, 1742-1746. doi: 10.1086/315078
23. Campanella, G. S., Tager, A. M., El Khoury, J. K., Thomas, S. Y., Abrazinski, T. A., Manice, L. A., et al. (2008). Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proc. Natl. Acad. Sci. U.S.A. 105, 4814-4819. doi: 10.1073/pnas.08015 44105
24. Chan-Ling, T., Neill, A. L., Hunt, N. H. (1992). Early microvascular changes in murine cerebral detected using retinal wholemounts. Am. J. Pathol. 140, 1121-1130.
25. Clark, C. J., Mackay, G. M., Smythe, G. A., Bustamante, S., Stone, T. W., Phillips, R. S. (2005). Prolonged survival of a murine model of cerebral malaria by kynurenine pathway inhibition. Infect. Immun. 73, 5249-5251. doi: 10.1128/IAI.73.8.5249-5251.2005
26. Clark, I. A., Rockett, K. A. (1994). The cytokine theory of human cerebral malaria. Parasitol. Today 10, 410-412. doi: 10.1016/0169-4758(94) 90237-2
27. Claser, C., Malleret, B., Gun, S. Y., Wong, A. Y., Chang, Z. W., Teo, P., et al. (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. doi: 10.1371/journal.pone. 0018720
28. Combes, V., Coltel, N., Faille, D., Wassmer, S. C., Grau, G. E. (2006). Cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier. Int. J. Parasitol. 36, 541-546. doi: 10.1016/j.ijpara.2006.02.005
29. Combes, V., El-Assaad, F., Faille, D., Jambou, R., Hunt, N. H., Grau, G. E. (2010). Microvesiculation and cell interactions at the brain-endothelial interface in cerebral malaria pathogenesis. Prog. Neurobiol. 91, 140-151. doi: 10.1016/j.pneurobio.2010.01.007
30. Combes, V., Guillemin, G. J., Chan-Ling, T., Hunt, N. H., Grau, G. E. R. (2012). The crossroads of neuroinflammation in infectious diseases: endothelial cells and astrocytes. Trends Parasitol. 28, 311-319. doi: 10.1016/j.pt.2012. 05.008
31. Cunnington, A. J., Riley, E. M., Walther, M. (2013). Stuck in a rut? Reconsidering the role of parasite sequestration in severe malaria syndromes. Trends Parasitol. 29, 585-592. doi: 10.1016/j.pt.2013.10.004
32. Das, B. S., Mohanty, S., Mishra, S. K., Patnaik, J. K., Satpathy, S. K., Mohanty, D., et al. (1991). Increased cerebrospinal fluid protein and lipid peroxidation products in patients with cerebral malaria. Trans. R. Soc. Trop. Med. Hyg. 85, 733-734. doi: 10.1016/0035-9203(91)90436-3
33. de Kossodo, S., Grau, G. E. (1993). Role of cytokines and adhesion molecules in malaria immunopathology. Stem Cells 11, 41-48. doi: 10.1002/stem.55301 10108
34. de Kossodo, S., Monso, C., Juillard, P., Velu, T., Goldman, M., Grau, G. E. (1997). Interleukin-10 modulates susceptibility in experimental cerebral malaria. Immunology 91, 536-540. doi: 10.1046/j.1365-2567.1997.00290.x
35. deWalick, S., Amante, F. H., McSweeney, K. A., Randall, L. M., Stanley, A. C., Haque, A., et al. (2007). Cutting edge: conventional dendritic cells are the critical APC required for the induction of experimental cerebral malaria. J. Immunol. 178, 6033-6037. doi: 10.4049/jimmunol.178.10.6033
36. D'Ombrain, M. C., Hansen, D. S., Simpson, K. M., Schofield, L. (2007). gammadelta-T cells expressing NK receptors predominate over NK cells and conventional T cells in the innate IFN-gamma response to Plasmodium falciparum malaria. Eur. J. Immunol. 37, 1864-1873. doi: 10.1002/eji.200636889
37. El-Assaad, F., Wheway, J., Mitchell, A. J., Lou, J., Hunt, N. H., Combes, V., et al. (2013). Cytoadherence of Plasmodium berghei-infected red blood cells to murine brain and lung microvascular endothelial cells in vitro. Infect. Immun. 81, 3984-3991. doi: 10.1128/IAI.00428-13
38. 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. J. Exp. Med. 195, 1371-1377. doi: 10.1084/jem.20020128
39. Favre, N., Da Laperousaz, C., Ryffel, B., Weiss, N. A., Imhof, B. A., Rudin, W., et al. (1999). Role of ICAM-1 (CD54) in the development of murine cerebral malaria. Microbes Infect. 1, 961-968. doi: 10.1016/S1286-4579(99)80513-9
40. Good, M. F., Xu, H., Wykes, M., Engwerda, C. R. (2005). Development and regulation of cell-mediated immune responses to the blood stages of malaria: implications for vaccine research. Annu. Rev. Immunol. 23, 69-99. doi: 10.1146/annurev.immunol.23.021704.115638
41. Grau, G. E., De Kossodo, S. (1994). Cerebral malaria: mediators, mechanical obstruction or more? Parasitol. Today 10, 408-410. doi: 10.1016/0169- 4758(94)90236-4
42. Grau, G. E., de Moerloose, P., Bulla, O., Lou, J., Lei, Z., Reber, G., et al. (1997). Haemostatic properties of human pulmonary and cerebral microvascular endothelial cells. Thromb. Haemost. 77, 585-590.
43. Grau, G. E., Heremans, H., Piguet, P. F., Pointaire, P., Lambert, P. H., Billiau, A., et al. (1989). Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumour necrosis factor. Proc. Natl. Acad. Sci. U.S.A. 86, 5572-5574. doi: 10.1073/pnas. 86.14.5572
44. Grau, G. E., Mackenzie, C. D., Carr, R. A., Redard, M., Pizzolato, G., Allasia, C., et al. (2003). Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria.J. Infect. Dis. 187, 461-466. doi: 10.1086/367960
45. Grau, G. E., Piguet, P. F., Engers, H. D., Louis, J. A., Vassalli, P., Lambert, P. H. (1986). L3T4+ lymphocytes play a major role in the pathogenesis of murine cerebral malaria.J. Immunol. 137, 2348-2354.
46. Hansen, A. M., Ball, H. J., Mitchell, A. J., Miu, J., Takikawa, O., Hunt, N. H. (2004). Increased expression of indoleamine 2,3-dioxygenase in murine malaria infection is predominantly localised to the vascular endothelium. Int. J. Parasitol. 34, 1309-1319. doi: 10.1016/j.ijpara.2004.07.008
47. 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 bergheimediated cerebral malaria. J. Immunol. 178, 5779-5788. doi: 10.4049/jimmunol. 178.9.5779
48. Hansen, D. S., Evans, K. J., D'Ombrain, M. C., Bernard, N. J., Sexton, A. C., Buckingham, L., et al. (2005). The natural killer complex regulates severe malarial pathogenesis and influences acquired immune responses to Plasmodium berghei ANKA. Infect. Immun. 73, 2288-2297. doi: 10.1128/IAI.73.4.2288- 2297.2005
49. Hansen, D. S., Ryg-Cornejo, V., Ioannidis, L. J., Chiu, C. Y., Ly, A., Nie, C. Q., et al. (2014). The contribution of natural killer complex loci to the development of experimental cerebral malaria. PLoS ONE 9:e93268. doi: 10.1371/journal. pone.0093268
50. Hansen, D. S., Siomos, M. A., Buckingham, L., Scalzo, A. A., Schofield, L. (2003). Regulation of murine cerebral malaria pathogenesis by CD1drestricted NKT cells and the natural killer complex. Immunity 18, 391-402. doi: 10.1016/S1074-7613(03)00052-9
51. Haque, A., Best, S. E., Unosson, K., Amante, E H., de Labastida, F., Anstey, N. M., et al. (2011). Granzyme B expression by CD8+T cells is required for the development of experimental cerebral malaria.J. Immunol. 186, 6148-6156. doi: 10.4049/jimmunol.1003955
52. Hempel, C., Combes, V., Hunt, N. H., Kurtzhals, J. A., Grau, G. E. (2011). CNS hypoxia is more pronounced in murine cerebral than noncerebral malaria and is reversed by erythropoietin. Am. J. Pathol. 179, 1939-1950. doi: 10.1016/j.ajpath.2011.06.027
53. Hensmann, M., Kwiatkowski, D. (2001). Cellular basis of early cytokine response to Plasmodium falciparum. Infect. Immun. 69, 2364-2371. doi: 10.1128/IAI.69.4.2364-2371.2001
54. Ho, M., Schollaardt, T., Niu, X., Looareesuwan, S., Patel, K. D., Kubes, P. (1998b). Characterization of Plasmodium falciparum-infected erythrocyte and P-selectin interaction under flow conditions. Blood. 91, 4803-4809.
55. Ho, M., Schollaardt, T., Snape, S., Looareesuwan, S., Suntharasamai, P., White, N. J. (1998a). Endogenous interleukin-10 modulates proinflammatory response in Plasmodium falciparum malaria. J. Infect. Dis. 178, 520-525. doi: 10.1086/515640
56. Horowitz, A., Newman, K. C., Evans, J. H., Korbel, D. S., Davis, D. M., Riley, E. M. (2010). Cross-talk between T cells and NK cells generates rapid effector responses to Plasmodium falciparum-infected erythrocytes. J. Immunol. 184, 6043-6052. doi: 10.4049/jimmunol.1000106
57. Howland, S. W., Poh, C. M., Gun, S. Y., Claser, C., Malleret, B., Shastri, N., et al. (2013). Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria. EMBO Mol. Med. 5, 984-999. doi: 10.1002/emmm.2012 02273
58. Hunt, N. H., Golenser, J., Chan-Ling, T., Parekh, S., Rae, C., Potter, S., et al. (2006). Immunopathogenesis of cerebral malaria. Int. J. Parasitol. 36, 569-582. doi: 10.1016/j.ijpara.2006.02.016
59. Hunt, N. H., Grau, G. E. (2003). Cytokines: accelerators and brakes in the pathogenesis of cerebral malaria. Trends Immunol. 24, 491-499. doi: 10.1016/S1471-4906(03)00229-1
60. Jelic, S., Le Jemtel, T. H. (2008). Inflammation, oxidative stress, the vascular endothelium in obstructive sleep apnea. Trends Cardiovasc. Med. 18, 253-260. doi: 10.1016/j.tcm.2008.11.008
61. John, C. C., Bangirana, P., Byarugaba, J., Opoka, R. O., Idro, R., Jurek, A. M., et al. (2008). Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics 122, e92-e99. doi: 10.1542/peds.2007-3709
62. John, G. R., Lee, S. C., Brosnan, C. E (2003). Cytokines: powerful regulators of glial cell activation. Neuros cientist 9, 10-22. doi: 10.1177/1073858402239587
63. Khaw, L. T., Ball, H. J., Golenser, J., Combes, V., Grau, G. E., Wheway, J., et al. (2013). Endothelial cells potentiate interferon-gamma production in a novel tripartite culture model of human cerebral malaria. PLoS ONE 8:e69521. doi: 10.1371/journal.pone.0069521
64. Kihara, M., Carter, J. A., Newton, C. R. (2006). The effect of Plasmodium falciparum on cognition: a systematic review. Trop. Med. Int. Health 11, 386-397. doi: 10.1111/j.1365-3156.2006.01579.x
65. Korbel, D. S., Newman, K. C., Almeida, C. R., Davis, D. M., Riley, E. M. (2005). Heterogeneous human NK cell responses to Plasmodium falciparuminfected erythrocytes.J. Immunol. 175, 7466-7473. doi: 10.4049/jimmunol.175. 11.7466
66. Kwiatkowski, D. P. (2005). How malaria has affected the human genome and what human genetics can teach us about malaria. Am. J. Hum. Genet. 77, 171-192. doi: 10.1086/432519
67. Langhorne, J., Buffet, P., Galinski, M., Good, M., Harty, J., Leroy, D., et al. (2011). The relevance of non-human primate and rodent malaria models for humans. Malar. J. 10:23. doi: 10.1186/1475-2875-10-23
68. Latham, S. L., Chaponnier, C., Dugina, V., Couraud, P. O., Grau, G. E., Combes, V. (2013). Cooperation between beta- and gamma-cytoplasmic actins in the mechanical regulation of endothelial microparticle formation. FASEB J. 27, 672-683. doi: 10.1096/fj.12-216531
69. Lau, L. S., Fernandez Ruiz, D., Davey, G. M., de Koning-Ward, T. F., Papenfuss, A. T., Carbone, F. R., et al. (2011). Blood-stage Plasmodium berghei infection generates a potent, specific CD8+T-cell response despite residence largely in cells lacking MHC I processing machinery. J. Infect. Dis. 204, 1989-1996. doi: 10.1093/infdis/jir656
70. Liberto, C. M., Albrecht, P. J., Herx, L. M., Yong, V. W., Levison, S. W. (2004). Pro-regenerative properties of cytokine-activated astrocytes. J. Neurochem. 89, 1092-1100. doi: 10.1111/j.1471-4159.2004.02420.x
71. Lou, J., Donati, Y. R., Juillard, P., Giroud, C., Vesin, C., Mili, N., et al. (1997). Platelets play an important role in TNF-induced microvascular endothelial cell pathology. Am. J. Pathol. 151, 1397-1405.
72. Lovegrove, E E., Gharib, S. A., Patel, S. N., Hawkes, C. A., Kain, K. C., Liles, W. C. (2007). Expression microarray analysis implicates apoptosis and interferonresponsive mechanisms in susceptibility to experimental cerebral malaria. Am. J. Pathol. 171, 1894-1903. doi: 10.2353/ajpath.2007.070630
73. Lundie, R. J., de Koning-Ward, T. F., Davey, G. M., Nie, C. Q., Hansen, D. S., Lau, L. S., et al. (2008). Blood-stage Plasmodium infection induces CD8+T lymphocytes to parasite-expressed antigens, largely regulated by CD8alpha+ dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 105, 14509-14514. doi: 10.1073/pnas.0806727105
74. Mackintosh, C. L., Beeson, J. G., Marsh, K. (2004). Clinical features and pathogenesis of severe malaria. Trends Parasitol. 20, 597-603. doi: 10.1016/j.pt.2004.09.006
75. McCall, M. B., Sauerwein, R. W. (2010). Interferon-gamma-central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria.J. Leukoc. Biol. 88, 1131-1143. doi: 10.1189/jlb.0310137
76. McQuillan, J. A., Mitchell, A. J., Ho, Y. F., Combes, V., Ball, H. J., Golenser, J., et al. (2011). Coincident parasite and CD8 T cell sequestration is required for development of experimental cerebral malaria. Int. J. Parasitol. 41, 155-163. doi: 10.1016/j.ijpara.2010.08.003
77. Medana, I. M., Chan-Ling, T., Hunt, N. H. (1996). Redistribution and degeneration of retinal astrocytes in experimental murine cerebral malaria: relationship to disruption of the blood-retinal barrier. Glia 16, 51-64.
78. Medana, I. M., Day, N. P., Hien, T. T., Mai, N. T., Bethell, D., Phu, N. H., et al. (2002). Axonal injury in cerebral malaria. Am. J. Pathol. 160, 655-666. doi: 10.1016/S0002-9440(10)64885-7
79. Medana, I. M., Day, N. P., Salahifar-Sabet, H., Stocker, R., Smythe, G., Bwanaisa, L., et al. (2003). Metabolites of the kynurenine pathway of tryptophan metabolism in the cerebrospinal fluid of Malawian children with malaria. J. Infect. Dis. 188, 844-849. doi: 10.1086/377583
80. Medana, I. M., Idro, R., Newton, C. R. (2007). Axonal and astrocyte injury markers in the cerebrospinal fluid of Kenyan children with severe malaria. J. Neurol Sci. 258, 93-98. doi: 10.1016/j.jns.2007.03.005
81. Miller, C. H., Maher, S. G., Young, H. A. (2009). Clinical use of interferon-gamma. Ann. N.Y. Acad. Sci. 1182, 69-79. doi: 10.1111/j.1749- 6632.2009.05069.x
82. Mitchell, A. J., Yau, B., McQuillan, J. A., Ball, H. J., Too, L. K., Abtin, A., et al. (2012). Inflammasome-dependent IFN-gamma drives pathogenesis in streptococcus pneumoniae meningitis.J. Immunol. 189, 4970-4980. doi: 10.4049/jimmunol. 1201687
83. Miu, J., Ball, H. J., Mellor, A. L., Hunt, N. H. (2009). Effect of indoleamine dioxygenase-1 deficiency and kynurenine pathway inhibition on murine cerebral malaria. Int. J. Parasitol. 39, 363-370. doi: 10.1016/j.ijpara.2008.10.005
84. Miu, J., Hunt, N. H., Ball, H. J. (2008b). Predominance of interferon-related responses in the brain during murine malaria, as identified by microarray analysis. Infect. Immun. 76, 1812-1824. doi: 10.1128/IAI.01650-07
85. Miu, J., Mitchell, A. J., Muller, M., Carter, S. L., Manders, P. M., McQuillan, J. A., et al. (2008a). Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. J. Immunol. 180, 1217-1230. doi: 10.4049/jimmunol. 180.2.1217
86. Molyneux, M. E., Taylor, T. E., Wirima, J. J., Borgstein, A. (1989). Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q. J. Med. 71, 441-459.
87. Morrell, C. N., Srivastava, K., Swaim, A., Lee, M. T., Chen, J., Nagineni, C., et al. (2011). Beta interferon suppresses the development of experimental cerebral malaria. Infect. Immun. 79, 1750-1758. doi: 10.1128/IAI.00810-10
88. Nedergaard, M., Dirnagl, U. (2005). Role of glial cells in cerebral ischemia. Glia 50, 281-286. doi: 10.1002/glia.20205
89. Newman, K. C., Korbel, D. S., Hafalla, J. C., Riley, E. M. (2006). Cross-talk with myeloid accessory cells regulates human natural killer cell interferon-gamma responses to malaria. PLoS Pathog. 2:e118. doi: 10.1371/journal.ppat.0020118
90. Newton, C. R., Hien, T. T., White, N. (2000). Cerebral malaria. J. Neurol. Neurosurg. Psychiatr. 69,433-441. doi: 10.1136/jnnp.69.4.433
91. Nie, C. Q., Bernard, N. J., Norman, M. U., Amante, E H., Lundie, R. J., Crabb, B. S., et al. (2009). IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection. PLoS Pathog. 5:e1000369. doi: 10.1371/journal.ppat.1000369
92. 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. doi: 10.1128/IAI.01783-06
93. Nitcheu, J., Bonduelle, O., Combadiere, C., Tefit, M., Seilhean, D., Mazier, D., et al. (2003). Perforin-dependent brain-infiltrating cytotoxic CD8(+) T lymphocytes mediate experimental cerebral malaria pathogenesis. J. Immunol. 170, 2221-2228. doi: 10.4049/jimmunol.170.4.2221
94. Omer, F. M., Riley, E. M. (1998). Transforming growth factor beta production is inversely correlated with severity of murine malaria infection. J. Exp. Med. 188, 39-48. doi: 10.1084/jem.188.1.39
95. Palomo, J., Fauconnier, M., Coquard, L., Gilles, M., Meme, S., Szeremeta, F., et al. (2013). Type I interferons contribute to experimental cerebral malaria development in response to sporozoite or blood-stage Plasmodium berghei ANKA. (2013). Eur. J. Immunol. 43, 2683-2695. doi: 10.1002/eji.201343327
96. Panickar, K. S., Norenberg, M. D. (2005). Astrocytes in cerebral ischemic injury: Morphological and general considerations. Glia 50, 287-298. doi: 10.1002/glia.20181
97. Parekh, S. B., Bubb, W. A., Hunt, N. H., Rae, C. (2006). Brain metabolic markers reflect susceptibility status in cytokine gene knockout mice with murine cerebral malaria. Int. J. Parasitol. 36, 1409-1418. doi: 10.1016/j.ijpara.2006.07.004
98. Patnaik, J. K., Das, B. S., Mishra, S. K., Mohanty, S., Satpathy, S. K., Mohanty, D. (1994). Vascular clogging, mononuclear cell margination, enhanced pathogenesis of human cerebral malaria. Am. J. Trop. Med. Hyg. 51, 642-647.
99. Penet, M. F., Viola, A., Confort-Gouny, S., Le Fur, Y., Duhamel, G., Kober, F., et al. (2005). Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema. J. Neurosci. 25, 7352-7358. doi: 10.1523/JNEUROSCI.1002-05.2005
100. Petzelbauer, P., Bender, J. R., Wilson, J., Pober, J. S. (1993). Heterogeneity of dermal microvascular endothelial cell antigen expression and cytokine responsiveness in situ and in cell culture. J. Immunol. 151, 5062-5072.
101. Piva, L., Tetlak, P., Claser, C., Karjalainen, K., Renia, L., Ruedl, C. (2012). Cutting edge: Clec9A+ dendritic cells mediate the development of experimental cerebral malaria. J. Immunol. 189, 1128-1132. doi: 10.4049/jimmunol. 1201171
102. Ponsford, M. J., Medana, I. M., Prapansilp, P., Hien, T. T., Lee, S. J., Dondorp, A. M., et al. (2012). Sequestration and microvascular congestion are associated with coma in human cerebral malaria. J. Infect. Dis. 205, 663-671. doi: 10.1093/infdis/jir812
103. Potter, S., Chaudhri, G., Hansen, A., Hunt, N. H. (1999). Fas and perforin contribute to the pathogenesis of murine cerebral malaria. RedoxRep. 4, 333-335. doi: 10.1179/135100099101535070
104. Potter, S. M., Chan-Ling, T., Ball, H. J., Mitchell, A., Miu, J., Maluish, L., et al. (2006). Perforin-mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. Int. J. Parasitol. 36, 485-496. doi: 10.1016/j.ijpara.2005.12.005
105. Rae, C., McQuillan, J. A., Parekh, S. B., Bubb, W A., Weiser, S., Balcar, V. J., et al. (2004). Brain gene expression, metabolism, bioenergetics: interrelationships in murine models of cerebral and noncerebral malaria. FASEB J. 18, 499-510. doi: 10.1096/fj.03-0543com
106. Riley, E. M., Wahl, S., Perkins, D. J., Schofield, L. (2006). Regulating immunity to malaria. Parasite Immunol. 28, 35-49. doi: 10.1111/j.1365-3024.2006.00775.x
107. Rossi, D. J., Brady, J. D., Mohr, C. (2007). Astrocyte metabolism and signaling during brain ischemia. Nat. Neurosci. 10, 1377-1386. doi: 10.1038/nn2004
108. Rossi, D., Volterra, A. (2009). Astrocytic dysfunction: Insights on the role in neurodegeneration. Brain Res. Bull. 80, 224-232. doi: 10.1016/j.brainresbull.2009.07.012
109. Ryg-Cornejo, V., Nie, C. Q., Bernard, N. J., Lundie, R. J., Evans, K. J., Crabb, B. S., et al. (2013). NK cells and conventional dendritic cells engage in reciprocal activation for the induction of inflammatory responses during Plasmodium berghei ANKA infection. Immunobiology 218, 263-271. doi: 10.1016/j.imbio.2012.05.018
110. Saha, B., Jyothi Prasanna, S., Chandrasekar, B., Nandi, D. (2010). Gene modulation and immunoregulatory roles of interferon gamma. Cytokine 50, 1-14. doi: 10.1016/j.cyto.2009.11.021
111. Sanni, L. A., Rae, C., Maitland, A., Stocker, R., Hunt, N. H. (2001). Is ischemia involved in the pathogenesis of murine cerebral malaria? Am. J. Pathol. 159, 1105-1112. doi: 10.1016/S0002-9440(10)61786-5
112. Sanni, L. A., Thomas, S. R., Tattam, B. N., Moore, D. E., Chaudhri, G., Stocker, R., et al. (1998). Dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria. Am. J. Pathol. 152,611-619.
113. Schofield, L., Grau, G. E. (2005). Immunological processes in malaria pathogenesis. Nat. Rev. Immunol. 5, 722-735. doi: 10.1038/nri1686
114. Schroder, K., Hertzog, P. J., Ravasi, T., Hume, D. A. (2004). Interferon-gamma: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75, 163-189. doi: 10.1189/jlb.0603252
115. Takano, T., Oberheim, N., Cotrina, M. L., Nedergaard, M. (2009). Astrocytes and ischemic injury. Stroke 40(3 Suppl), S8-S12. doi: 10.1161/STROKEAHA.108.533166
116. Taylor, T. E., Fu, W. J., Carr, R. A., Whitten, R. O., Mueller, J. S., Fosiko, N. G., et al. (2004). Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat. Med. 10, 143-145. doi: 10.1038/nm986
117. Thumwood, C. M., Hunt, N. H., Clark, I. A., Cowden, W. B. (1988). Breakdown of the blood-brain barrier in murine cerebral malaria. Parasitology 96, 579-589. doi: 10.1017/S0031182000080203
118. Toro, G., andRoman, G. (1978). Cerebral malaria: disseminated vasculomyelinopathy. Arch Neurol 35, 271-275. doi: 10.1001/archneur.1978.00500290017004
119. Trendelenburg, G., Dirnagl, U. (2005). Neuroprotective role of astrocytes in cerebral ischemia: focus on ischemic preconditioning. Glia 50, 307-320. doi: 10.1002/glia.20204
120. Turner, G. D., Morrison, H., Jones, M., Davis, T. M., Looareesuwan, S., Buley, I. D., et al. (1994). An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am. J. Pathol. 145, 1057-1069.
121. Turner, L., Lavstsen, T., Berger, S. S., Wang, C. W., Petersen, J. E., Avril, M., et al. (2013). Severe malaria is associated with parasite binding to endothelial protein C receptor. Nature 498, 502-505. doi: 10.1038/nature12216
122. Udomsangpetch, R., Chivapat, S., Viriyavejakul, P., Riganti, M., Wilairatana, P., Pongponratin, E., et al. (1997). Involvement of cytokines in the histopathology of cerebral malaria. Am. J. Trop. Med. Hyg. 57, 501-506.
123. Van den Steen, P. E., Deroost, K., Van Aelst, I., Geurts, N., Martens, E., Struyf, S., et al. (2008). CXCR3 determines strain susceptibility to murine cerebral malaria by mediating T lymphocyte migration toward IFN-gammainduced chemokines. Eur. J. Immunol. 38, 1082-1095. doi: 10.1002/eji.200 737906
124. van der Heyde, H. C., Bauer, P., Sun, G., Chang, W. L., Yin, L., Fuseler, J., et al. (2001). Assessing vascular permeability during experimental cerebral malaria by a radiolabeled monoclonal antibody technique. Infect. Immun. 69, 3460-3465. doi:10.1128/IAI.69.5.3460-3465.2001
125. Verkhrasky, A., Krishtal, O. A., Burnstock, G. (2009). Purinoceptors on neuroglia. Mol. Neurobiol. 39, 190-208. doi: 10.1007/s12035-009-8063-2
126. Verra, F., Mangano, V. D., Modiano, D. (2009). Genetics of susceptibility to Plasmodium falciparum: from classical malaria resistance genes towards genome-wide association studies. Parasite Immunol. 31, 234-253. doi: 10.1111/j.1365-3024.2009.01106.x
127. Vigario, A. M., Belnoue, E., Gruner, A. C., Mauduit, M., Kayibanda, M., Deschemin, J. C., et al. (2007). Recombinant human IFN-alpha inhibits cerebral malaria and reduces parasite burden in mice. J. Immunol. 178, 6416-6425. doi: 10.4049/jimmunol.178.10.6416
128. Villegas-Mendez, A., Greig, R., Shaw, T. N., de Souza, J. B., Gwyer Findlay, E., Stumhofer, J. S., et al. (2012). IFN-gamma-producing CD4+T cells promote experimental cerebral malaria by modulating CD8+T cell accumulation within the brain.J. Immunol. 189, 968-979. doi: 10.4049/jimmunol.1200688
129. Wahl, S. M., Feldman, G. M., McCarthy, J. B. (1996). Regulation of leukocyte adhesion and signaling in inflammation and disease. J. Leukoc. Biol. 59, 789-796.
130. Walther, M., Woodruff, J., Edele, F., Jeffries, D., Tongren, J. E., King, E., et al. (2006). Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes.J. Immunol. 177, 5736-5745. doi: 10.4049/jimmunol.177.8.5736
131. Wang, Y., Liu, H., McKenzie, G., Witting, P. K., Stasch, J. P., Hahn, M., et al. (2010). Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Nat. Med. 16, 279-285. doi: 10.1038/ nm.2092
132. Warrell, D. A., Veal, N., Chanthavanich, P., Karbwang, J., White, N. J., Looareesuwan, S., et al. (1988). Cerebral anaerobic glycolysis and reduced cerebral oxygen transport in human cerebral malaria. Lancet 2, 534-537. doi: 10.1016/S0140-6736(88)92658-X
133. Wassmer, S. C., Combes, V., Candal, F. J., Juhan-Vague, I., Grau, G. E. (2006a). Platelets potentiate brain endothelial alterations induced by Plasmodium falciparum. Infect. Immun. 74, 645-653. doi: 10.1128/IAI.74.1.645-653.2006
134. Wassmer, S. C., de Souza, J. B., Frere, C., Candal, F. J., Juhan-Vague, I., Grau, G. E. (2006b). TGF-beta1 released from activated platelets can induce TNF-stimulated human brain endothelium apoptosis: a new mechanism for microvascular lesion during cerebral malaria. J. Immunol. 176, 1180-1184. doi: 10.4049/jimmunol.176.2.1180
135. Wassmer, S. C., Lepolard, C., Traore, B., Pouvelle, B., Gysin, J., Grau, G. E. (2004). Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells. J. Infect. Dis. 189, 180-189. doi: 10.1086/380761
136. Weiser, S., Miu, J., Ball, H. J., Hunt, N. H. (2007). Interferon-gamma synergises with tumour necrosis factor and lymphotoxin-alpha to enhance the mRNA and protein expression of adhesion molecules in mouse brain endothelial cells. Cytokine 37, 84-91. doi: 10.1016/j.cyto.2007.02.021
137. White, N. J., Turner, G. D., Day, N. P., Dondorp, A. M. (2013). Lethal malaria: Marchiafava and Bignami were right. J. Infect. Dis. 208, 192-198. doi: 10.1093/infdis/jit116
138. White, N. J., Warrell, D. A., Looareesuwan, S., Chanthavanich, P., Phillips, R. E., Pongpaew, P. (1985). Pathophysiological and prognostic significance of cerebrospinal-fluid lactate in cerebral malaria. Lancet 1, 776-778. doi: 10.1016/S0140-6736(85)91445-X
139. White, V A., Lewallen, S., Beare, N. A., Molyneux, M. E., Taylor, T. E. (2009). Retinal pathology of pediatric cerebral malaria in Malawi. PLoS ONE 4:e4317. doi: 10.1371/journal.pone.0004317
140. White, V A., Lewallen, S., Beare, N., Kayira, K., Carr, R. A., Taylor, T. E. (2001). Correlation of retinal haemorrhages with brain haemorrhages in children dying of cerebral malaria in Malawi. Trans. R. Soc. Trop. Med. Hyg. 95, 618-621. doi: 10.1016/S0035-9203(01)90097-5
141. Wilson, N., Driss, A., Solomon, W., Dickinson-Copeland, C., Salifu, H., Jain, V., et al. (2013). CXCL10 gene promoter polymorphism -1447AG correlates with plasma CXCL10 levels and is associated with male susceptibility to cerebral malaria. PLoS ONE 8:e81329. doi: 10.1371/journal.pone.0081329
142. Yanez, D. M., Manning, D. D., Cooley, A. J., Weidanz, W. P., Van der Heyde, H. C. (1996). Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria. J. Immunol. 157, 1620-1624.