Programmed Cell Death during Malaria Parasite Infection of the Vertebrate Host and Mosquito Vector

  • Luke A. Baton
  • Emma Warr
  • Seth A. Hoffman
  • George Dimopoulos
Part of the Molecular Biology Intelligence Unit book series (MBIU)


In recent years, there has been an increasing awareness of the role of programmed cell death (PCD) in the malaria parasite’s infection of its vertebrate host and mosquito vector. Although the evidence that PCD occurs within malaria parasites themselves is currently limited and controversial, a significant body of research now indicates that PCD of both vertebrate host and mosquito vector cells plays an important, if still incompletely understood, role during infection with this parasite. A greater understanding of the role of PCD during malaria infection of the vertebrate host and mosquito vector may lead to the development of novel intervention strategies that can reduce the burden of the disease. Here we review the current evidence for the existence of PCD within malaria parasites themselves and discuss the recent fascinating advances in our understanding of the occurrence of PCD in vertebrate host and mosquito vector cells during malaria infection.


Malaria Parasite Plasmodium Falciparum Malaria Infection Cerebral Malaria Mosquito Vector 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Garnham PCC. Malaria Parasites and other Haemosporidia. Oxford: Blackwell Scientific Publications; 1966.Google Scholar
  2. 2.
    Hay SI, Guerra CA, Tatem AJ et al. The global distribution and population at risk of malaria: past, present and future. Lancet Infect Dis 2004; 4:327–336.PubMedGoogle Scholar
  3. 3.
    Snow RW, Guerra CA, Noor AM et al. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 2005; 434:214–217.PubMedGoogle Scholar
  4. 4.
    Greenwood BM, Bojang K, Whitty CJ et al. Malaria. Lancet 2005; 365:1487–1498.PubMedGoogle Scholar
  5. 5.
    Hyde JE. Drug-resistant malaria. Trends Parasitol 2005; 21:494–498.PubMedGoogle Scholar
  6. 6.
    Hemingway J, Hawkes NJ, McCarroll L et al. The molecular basis of insecticide resistance in mosquitoes. Insect Biochem Mol Biol 2004; 34:653–665.PubMedGoogle Scholar
  7. 7.
    Bannister L, Mitchell G. The ins, outs and roundabouts of malaria. Trends Parasitol 2003; 19:209–213. See for computer animation.PubMedGoogle Scholar
  8. 8.
    Baton LA, Ranford-Cartwright LC. Spreading the seeds of million-murdering death: metamorphoses of malaria in the mosquito. Trends Parasitol 2005; 21:573–580. See Appendix—Supplementary data at to download computer animation.PubMedGoogle Scholar
  9. 9.
    Frevert U. Sneaking in through the back entrance: the biology of malaria liver stages. Trends Parasitol 2004; 20:417–424. See for computer animation.PubMedGoogle Scholar
  10. 10.
    Frischknecht F, Baldacci P, Martin B et al. Imaging movement of malaria parasites during transmission by Anopheles mosquitoes. Cell Microbiol 2004; 6:687–694.PubMedGoogle Scholar
  11. 11.
    Vanderberg JP, Frevert U. Intravital microscopy demonstrating antibody-mediated immobilisation of Plasmodium berghei sporozoites injected into skin by mosquitoes. Int J Parasitol 2004; 34:991–996.PubMedGoogle Scholar
  12. 12.
    Amino R, Thiberge S, Martin B et al. Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nat Med 2006; 12:220–224.PubMedGoogle Scholar
  13. 13.
    Frevert U, Engelmann S, Zougbede S et al. Intravital observation of Plasmodium berghei sporozoite infection of the liver. PLoS Biol 2005; 3:e.192.Google Scholar
  14. 14.
    Ameisen JC. The origin of programmed cell death. Science 1996; 272:1278–1279.PubMedGoogle Scholar
  15. 15.
    Ameisen JC. On the origin, evolution and nature of programmed cell death: a timeline of four billion years. Cell Death Differ 2002; 9:367–393.PubMedGoogle Scholar
  16. 16.
    Ameisen JC. Looking for death at the core of life in the light of evolution. Cell Death Differ 2004; 11:4–10.PubMedGoogle Scholar
  17. 17.
    Broker LE, Kruyt FA, Giaccone G. Cell death independent of caspases: a review. Clin Cancer Res 2005; 11:3155–3162.PubMedGoogle Scholar
  18. 18.
    Meier P, Finch A, Evan G. Apoptosis in development. Nature 2000; 407:796–801.PubMedGoogle Scholar
  19. 19.
    Vaux DL, Haecker G, Strasser A. An evolutionary perspective on apoptosis. Cell 1994; 76:777–779.PubMedGoogle Scholar
  20. 20.
    Williams GT. Programmed cell death: a fundamental protective response to pathogens. Trends Microbiol 1994; 2:463–464.PubMedGoogle Scholar
  21. 21.
    James ER, Green DR. Manipulation of apoptosis in the host-parasite interaction. Trends Parasitol 2004; 20:280–287.PubMedGoogle Scholar
  22. 22.
    Hamilton WD. Narrow Roads of Gene Land, Volume 1: Evolution of Social Behavior. Oxford: Oxford University Press: 1996.Google Scholar
  23. 23.
    Babiker HA, Ranford-Cartwright LC, Currie D et al. Random mating in a natural population of the malaria parasite Plasmodium falciparum. Parasitology 1994; 109:413–421.PubMedGoogle Scholar
  24. 24.
    Babiker HA, Charlwood JD, Smith T et al. Gene flow and cross-mating in Plasmodium falciparum in households in a Tanzanian village. Parasitology 1995; 111:433–442.PubMedGoogle Scholar
  25. 25.
    Walliker D. Malaria parasites: randomly interbreeding or clonal populations? Parasitol Today 1991; 7:232–235.PubMedGoogle Scholar
  26. 26.
    Anderson TJ, Haubold B, Williams JT et al. Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum. Mol Biol Evol 2000; 17:1467–1482.PubMedGoogle Scholar
  27. 27.
    Babiker HA, Walliker D. Current views on the population structure of Plasmodium falciparum: Implications for control. Parasitol Today 1997; 13:262–267.PubMedGoogle Scholar
  28. 28.
    Paul RE, Packer MJ, Walmsley M et al. Mating patterns in malaria parasite populations of Papua New Guinea. Science 1995; 269:1709–1711.PubMedGoogle Scholar
  29. 29.
    Razakandrainibe FG, Durand P, Koella JC et al. Clonal population structure of the malaria agent Plasmodium falciparum in high-infection regions. Proc Natl Acad Sci USA 2005; 102:17388–17393.PubMedGoogle Scholar
  30. 30.
    Walliker D, Babiker H, Ranford-Cartwright L. The genetic structure of malaria parasite populations. In: Sherman IW, ed. Malaria: Parasite Biology, Pathogenesis and Protection. Washington, DC: American Society for Microbiology Press; 1998:235–52.Google Scholar
  31. 31.
    Dawkins R. The Selfish Gene. 2nd ed. Oxford: Oxford University Press; 1989.Google Scholar
  32. 32.
    Dieckmann U, Metz JAJ, Sabelis MW et al. eds. Adaptive Dynamics of Infectious Diseases: In Pursuit of Virulence Management. Cambridge: Cambridge University Press; 2002.Google Scholar
  33. 33.
    Ewald PW. Evolution of Infectious Disease. New York: Oxford University Press; 1994.Google Scholar
  34. 34.
    Sober E, Wilson DS. Unto Others: The Evolution and Psychology of Unselfish Behavior. Cambridge: Harvard University Press; 1998.Google Scholar
  35. 35.
    Deponte M, Becker K. Plasmodium falciparum—do killers commit suicide? Trends Parasitol 2004; 20:165–169.PubMedGoogle Scholar
  36. 36.
    Paul REL, Ariey F, Robert V. The evolutionary ecology of Plasmodium. Ecol Lett 2003; 6:866–880.Google Scholar
  37. 37.
    Dyer M, Day KP. Regulation of the rate of asexual growth and commitment to sexual development by diffusible factors from in vitro cultures of Plasmodium falciparum. Am J Trop Med Hyg 2003; 68:403–409.PubMedGoogle Scholar
  38. 38.
    Hurd H, Carter V, Nacer A. Interactions between malaria and mosquitoes: the role of apoptosis in parasite establishment and vector response to infection. Curr Top Microbiol Immunol 2005; 289:185–217.PubMedGoogle Scholar
  39. 39.
    Hurd H, Carter V. The role of programmed cell death in Plasmodium-mosquito interactions. Int J Parasitol 2004; 34:1459–1472.PubMedGoogle Scholar
  40. 40.
    Uren AG, O’Rourke K, Aravind LA et al. Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma. Mol Cell 2000; 6:961–967.PubMedGoogle Scholar
  41. 41.
    van de Sand C, Horstmann S, Schmidt A et al. The liver stage of Plasmodium berghei inhibits host cell apoptosis. Mol Microbiol 2005; 58:731–742.PubMedGoogle Scholar
  42. 42.
    Wu Y, Wang X, Liu X et al. Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite. Genome Res 2003; 13:601–616.PubMedGoogle Scholar
  43. 43.
    Sperandio S, Poksay K, de BI et al. Paraptosis: mediation by MAP kinases and inhibition by AIP-1/Alix. Cell Death Differ 2004; 11:1066–1075.PubMedGoogle Scholar
  44. 44.
    Ward P, Equinet L, Packer J et al. Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote. BMC Genomics 2004; 5:79.PubMedGoogle Scholar
  45. 45.
    Picot S, Burnod J, Bracchi V et al. Apoptosis related to chloroquine sensitivity of the human malaria parasite Plasmodium falciparum. Trans R Soc Trop Med Hyg 1997; 91:590–591.PubMedGoogle Scholar
  46. 46.
    Nyakeriga AM, Perlmann H, Hagstedt M et al. Drug-induced death of the asexual blood stages of Plasmodium falciparum occurs without typical signs of apoptosis. Microbes Infect 2006; in press.Google Scholar
  47. 47.
    Pankova-Kholmyansky I, Dagan A, Gold D et al. Ceramide mediates growth inhibition of the Plasmodium falciparum parasite. Cell Mol Life Sci 2003; 60:577–587.PubMedGoogle Scholar
  48. 48.
    Pettus BJ, Chalfant CE, Hannun YA. Ceramide in apoptosis: an overview and current perspectives. Biochim Biophys Acta 2002; 1585:114–125.PubMedGoogle Scholar
  49. 49.
    Al-Olayan EM, Williams GT, Hurd H. Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. Int J Parasitol 2002; 32:1133–1143.PubMedGoogle Scholar
  50. 50.
    Al-Olayan EM, Williams GT, Hurd H. Erratum to Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito [Int J Parasitol. 32(9) (2002) 1133–1143]. Int J Parasitol 2003; 33:105.Google Scholar
  51. 51.
    Leirião P, Albuquerque SS, Corso S et al. MGF/MET signalling protects Plasmodium-infected host cells from apoptosis. Cell Microbiol 2005; 7:603–609.PubMedGoogle Scholar
  52. 52.
    Carrolo M, Giordano S, Cabrita-Santos L et al. Hepatocyte growth factor and its receptor are required for malaria infection. Nat Med 2003; 9:1363–1369.PubMedGoogle Scholar
  53. 53.
    Leiriao P, Mota MM, Rodriguez A. Apoptotic Plasmodium-infected hepatocytes provide antigens to liver dendritic cells. J Infect Dis 2005; 191:1576–1581.PubMedGoogle Scholar
  54. 54.
    James E. Apoptosis: key to the attenuated malaria vaccine? J Infect Dis 2005; 191:1573–1575.PubMedGoogle Scholar
  55. 55.
    Leiriao P, Mota MM, Rodriguez A. Do apoptotic Plasmodium-infected hepatocytes initiate protective immune responses? Reply to Rénia et al. J Infect Dis 2006; 193:164–165.Google Scholar
  56. 56.
    Rénia L, Maranon C, Hosmalin A et al. Do apoptotic Plasmodium-infected hepatocytes initiate protective immune responses? J Infect Dis 2006; 193:163–164.PubMedGoogle Scholar
  57. 57.
    van Dijk MR, Douradinha B, Franke-Fayard B et al. Genetically attenuated, P36p-deficient malaria sporozoites induce protective immunity and apoptosis of infected liver cells. Proc Natl Acad Sci USA 2005; 102:12194–12199.PubMedGoogle Scholar
  58. 58.
    Heussler VT, Kuenzi P, Rottenberg S. Inhibition of apoptosis by intracellular protozoan parasites. Int J Parasitol 2001; 31:1166–1176.PubMedGoogle Scholar
  59. 59.
    Luder CG, Gross U, Lopes MF. Intracellular protozoan parasites and apoptosis: diverse strategies to modulate parasite-host interactions. Trends Parasitol 2001; 17:480–486.PubMedGoogle Scholar
  60. 60.
    Daugas E, Cande C, Kroemer G. Erythrocytes: death of a mummy. Cell Death Differ 2001; 8:1131–1133.PubMedGoogle Scholar
  61. 61.
    Lang KS, Lang PA, Bauer C et al. Mechanisms of suicidal erythrocyte death. Cell Physiol Biochem 2005; 15:195–202.PubMedGoogle Scholar
  62. 62.
    Berg CP, Engels IH, Rothbart A et al. Human mature red blood cells express caspase-3 and caspase-8, but are devoid of mitochondrial regulators of apoptosis. Cell Death Differ 2001; 8:1197–1206.PubMedGoogle Scholar
  63. 63.
    Bratosin D, Estaquier J, Petit F et al. Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria. Cell Death Differ 2001; 8:1143–1156.PubMedGoogle Scholar
  64. 64.
    Lang F, Lang KS, Wieder T et al. Cation channels, cell volume and the death of an erythrocyte. Pflugers Arch 2003;447:121–125.PubMedGoogle Scholar
  65. 65.
    Lang KS, Duranton C, Poehlmann H et al. Cation channels trigger apoptotic death of erythrocytes. Cell Death Differ 2003; 10:249–256.PubMedGoogle Scholar
  66. 66.
    Bratosin D, Mazurier J, Tissier JP et al. Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review. Biochimie 1998; 80:173–195.PubMedGoogle Scholar
  67. 67.
    Boas FE, Forman L, Beutler E. Phosphatidylserine exposure and red cell viability in red cell aging and in hemolytic anemia. Proc Natl Acad Sci USA 1998; 95:3077–3081.PubMedGoogle Scholar
  68. 68.
    Lang F, Lang PA, Lang KS et al. Channel-induced apoptosis of infected host cells—the case of malaria. Pflugers Arch 2004;448:319–324.PubMedGoogle Scholar
  69. 69.
    Brand VB, Sandu CD, Duranton C et al. Dependence of Plasmodium falciparum in vitro growth on the cation permeability of the human host erythrocyte. Cell Physiol Biochem 2003; 13:347–356.PubMedGoogle Scholar
  70. 70.
    Staines HM, Chang W, Ellory JC et al. Passive Ca2+ transport and Ca2+-dependent K+ transport in Plasmodium falciparum-infected red cells. J Membr Biol 1999; 172:13–24.PubMedGoogle Scholar
  71. 71.
    Weil M, Jacobson MD, Raff MC. Are caspases involved in the death of cells with a transcriptionally inactive nucleus? Sperm and chicken erythrocytes. J Cell Sci 1998; 111:2707–2715.PubMedGoogle Scholar
  72. 72.
    Berendt AR, Ferguson DJ, Newbold CI. Sequestration in Plasmodium falciparum malaria: sticky cells and sticky problems. Parasitol Today 1990; 6:247–254.PubMedGoogle Scholar
  73. 73.
    Newbold CI. Antigenic variation in Plasmodium falciparum: mechanisms and consequences. Curr Opin Microbiol 1999; 2:420–425.PubMedGoogle Scholar
  74. 74.
    Eda S, Sherman IW. Cytoadherence of malaria-infected red blood cells involves exposure of phosphatidylserine. Cell Physiol Biochem 2002; 12:373–384.PubMedGoogle Scholar
  75. 75.
    Lang KS, Roll B, Myssina S et al. Enhanced erythrocyte apoptosis in sickle cell anemia, thalassemia and glucose-6-phosphate dehydrogenase deficiency. Cell Physiol Biochem 2002; 12:365–372.PubMedGoogle Scholar
  76. 76.
    Beeson JG, Duffy PE. The immunology and pathogenesis of malaria during pregnancy. Curr Top Microbiol Immunol 2005; 297:187–227.PubMedGoogle Scholar
  77. 77.
    Grobusch MP, Kremsner PG. Uncomplicated malaria. Curr Top Microbiol Immunol 2005; 295:83–104.PubMedGoogle Scholar
  78. 78.
    Hunt NH, Golenser J, Chan-Ling T et al. Immunopathogenesis of cerebral malaria. Int J Parasitol 2006; 36:569–582.PubMedGoogle Scholar
  79. 79.
    Idro R, Jenkins NE, Newton CR. Pathogenesis, clinical features and neurological outcome of cerebral malaria. Lancet Neurol 2005; 4:827–840.PubMedGoogle Scholar
  80. 80.
    Planche T, Dzeing A, Ngou-Milama E et al. Metabolic complications of severe malaria. Curr Top Microbiol Immunol 2005; 295:105–136.PubMedGoogle Scholar
  81. 81.
    Roberts DJ, Casals-Pascual C, Weatherall DJ. The clinical and pathophysiological features of malaria anaemia. Curr Top Microbiol Immunol 2005; 295:137–167.PubMedGoogle Scholar
  82. 82.
    Schofield L, Grau GE. Immunological processes in malaria pathogenesis. Nat Rev Immunol 2005; 5:722–735.PubMedGoogle Scholar
  83. 83.
    Sherman IW, Eda S, Winograd E. Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. Microbes Infect 2003; 5:897–909.PubMedGoogle Scholar
  84. 84.
    Pino P, Taoufiq Z, Nitcheu J et al. Blood-brain barrier breakdown during cerebral malaria: suicide or murder? Thromb Haemost 2005; 94:336–340.PubMedGoogle Scholar
  85. 85.
    Hemmer CJ, Lehr HA, Westphal K et al. Plasmodium falciparum malaria: reduction of endothelial cell apoptosis in vitro. Infect Immun 2005; 73:1764–1770.PubMedGoogle Scholar
  86. 86.
    Pino P, Vouldoukis I, Dugas N et al. Redox-dependent apoptosis in human endothelial cells after adhesion of Plasmodium falciparum-infected erythrocytes. Ann N Y Acad Sci 2003; 1010:582–586.PubMedGoogle Scholar
  87. 87.
    Pino P, Vouldoukis I, Kolb JP et al. Plasmodium falciparum-infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis 2003; 187:1283–1290.PubMedGoogle Scholar
  88. 88.
    Potter S, Chan-Ling T, Ball HJ et al. Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. Int J Parasitol 2006; 36:485–496.PubMedGoogle Scholar
  89. 89.
    Wassmer SC, Combes V, Candal FJ et al. Platelets potentiate brain endothelial alterations induced by Plasmodium falciparum. Infect Immun 2006; 74:645–653.PubMedGoogle Scholar
  90. 90.
    Wiese L, Kurtzhals JA, Penkowa M. Neuronal apoptosis, metallothionein expression and proinflammatory responses during cerebral malaria in mice. Exp Neurol 2006.Google Scholar
  91. 91.
    Wassmer SC, de Souza JB, Frere C et al. TGF-β1 released from activated platelets can induce TNF-stimulated human brain endothelium apoptosis: a new mechanism for microvascular lesion during cerebral malaria. J Immunol 2006; 176:1180–1184.PubMedGoogle Scholar
  92. 92.
    Schluesener HJ, Kremsner PG, Meyermann R. Widespread expression of MRP8 and MRP14 in human cerebral malaria by microglial cells. Acta Neuropathol (Berl) 1998; 96:575–580.Google Scholar
  93. 93.
    Kaiser K, Texier A, Fetrandiz J et al. Recombinant human erythropoietin prevents the death of mice during cerebral malaria. J Infect Dis 2006; 193:987–995.PubMedGoogle Scholar
  94. 94.
    Medana IM, Mai NT, Day NP et al. Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria. Neuropathol Appl Neurobiol 2001; 27:421–433.PubMedGoogle Scholar
  95. 95.
    Potter SM, Chan-Ling T, Rosinova E et al. A role for Fas-Fas ligand interactions during the late-stage neuropathological processes of experimental cerebral malaria. J Neuroimmunol 2006; 173:96–107.PubMedGoogle Scholar
  96. 96.
    Crocker IP, Tanner OM, Myers JE et al. Syncytiotrophoblast degradation and the pathophysiology of the malaria-infected placenta. Placenta 2004; 25:273–282.PubMedGoogle Scholar
  97. 97.
    Guha M, Kumar S, Choubey V et al. Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway. FASEB J 2006.Google Scholar
  98. 98.
    Achtman AH, Bull PC, Stephens R et al. Longevity of the immune response and memory to blood-stage malaria infection. Curr Top Microbiol Immunol 2005; 297:71–102.PubMedGoogle Scholar
  99. 99.
    Balde AT, Sarthou JL, Roussilhon C. Acute Plasmodium falciparum infection is associated with increased percentages of apoptotic cells. Immunol Lett 1995; 46:59–62.PubMedGoogle Scholar
  100. 100.
    Balde AT, Aribot G, Tall A et al. Apoptosis modulation in mononuclear cells recovered from individuals exposed to Plasmodium falciparum infection. Parasite Immunol 2000; 22:307–318.PubMedGoogle Scholar
  101. 101.
    Kemp K, Akanmori BD, Adabayeri V et al. Cytokine production and apoptosis among T-cells from patients under treatment for Plasmodium falciparum malaria. Clin Exp Immunol 2002; 127:151–157.PubMedGoogle Scholar
  102. 102.
    Kemp K, Akanmori BD, Kurtzhals JA et al. Acute P. falciparum malaria induces a loss of CD28-T IFN-gamma producing cells. Parasite Immunol 2002; 24:545–548.PubMedGoogle Scholar
  103. 103.
    Kern P, Dietrich M, Hemmer C et al. Increased levels of soluble Fas ligand in serum in Plasmodium falciparum malaria. Infect Immun 2000; 68:3061–3063.PubMedGoogle Scholar
  104. 104.
    Matsumoto J, Kawai S, Terao K et al. Malaria infection induces rapid elevation of the soluble Fas ligand level in serum and subsequent T lymphocytopenia: possible factors responsible for the differences in susceptibility of two species of Macaca monkeys to Plasmodium coatneyi infection. Infect Immun 2000; 68:1183–1188.PubMedGoogle Scholar
  105. 105.
    Riccio EK, Junior IN, Riccio LR et al. Malaria associated apoptosis is not significantly correlated with either parasitemia or the number of previous malaria attacks. Parasitol Res 2003; 90:9–18.PubMedGoogle Scholar
  106. 106.
    ToureBalde A, Sarthou JL, Aribot G et al. Plasmodium falciparum induces apoptosis in human mononuclear cells. Infect Immun 1996; 64:744–750.Google Scholar
  107. 107.
    Hviid L, Kemp K. What is the cause of lymphopenia in malaria? Infect Immun 2000; 68:6087–6089.PubMedGoogle Scholar
  108. 108.
    Kemp K, Akanmori BD, Hviid L. West African donors have high percentages of activated cytokine producing T-cells that are prone to apoptosis. Clin Exp Immunol 2001; 126:69–75.PubMedGoogle Scholar
  109. 109.
    Helmby H, Jonsson G, Troye-Blomberg M. Cellular changes and apoptosis in the spleens and peripheral blood of mice infected with blood-stage Plasmodium chabaudi chabaudi AS. Infect Immun 2000; 68:1485–1490.PubMedGoogle Scholar
  110. 110.
    Sanchez-Torres L, Rodriguez-Ropon A, Aguilar-Medina M et al. Mouse splenic CD4+ and CD8+ T-cells undergo extensive apoptosis during a Plasmodium chabaudi chabaudi AS infection. Parasite Immunol 2001; 23:617–626.PubMedGoogle Scholar
  111. 111.
    Hirunpetcharat C, Good MF. Deletion of Plasmodium berghei-specific CD4+ T-cells adoptively transferred into recipient mice after challenge with homologous parasite. Proc Natl Acad Sci USA 1998; 95:1715–1720.PubMedGoogle Scholar
  112. 112.
    Wipasa J, Xu H, Stowers A et al. Apoptotic deletion of Th cells specific for the 19-kDa carboxyl-terminal fragment of merozoite surface protein 1 during malaria infection. J Immunol 2001; 167:3903–3909.PubMedGoogle Scholar
  113. 113.
    Xu H, Wipasa J, Yan H et al. The mechanism and significance of deletion of parasite-specific CD4(+) T-cells in malaria infection. J Exp Med 2002; 195:881–892.PubMedGoogle Scholar
  114. 114.
    Wykes MN, Zhou YH, Liu XQ et al. Plasmodium yoelii can ablate vaccine-induced long-term protection in mice. J Immunol 2005; 175:2510–2516.PubMedGoogle Scholar
  115. 115.
    Krzych U, Schwenk J. The dissection of CD8 T-cells during liver-stage infection. Curr Top Microbiol Immunol 2005; 297:1–24.PubMedGoogle Scholar
  116. 116.
    Baton LA, Ranford-Cartwright LC. Plasmodium falciparum ookinete invasion of the midgut epithelium of Anopheles stephensi is consistent with the Time Bomb model. Parasitology 2004; 129:663–676.PubMedGoogle Scholar
  117. 117.
    Han YS, Thompson J, Kafatos FC et al. Molecular interactions between Anopheles stephensi midgut cells and Plasmodium berghei: the time bomb theory of ookinete invasion of mosquitoes. EMBO J 2000; 19:6030–6040.PubMedGoogle Scholar
  118. 118.
    Vlachou D, Zimmermann T, Cantera R et al. Real-time, in vivo analysis of malaria ookinete locomotion and mosquito midgut invasion. Cell Microbiol 2004; 6:671–685.PubMedGoogle Scholar
  119. 119.
    Zieler H, Dvorak JA. Invasion in vitro of mosquito midgut cells by the malaria parasite proceeds by a conserved mechanism and results in death of the invaded midgut cells. Proc Natl Acad Sci USA 2000; 97:11516–11521.PubMedGoogle Scholar
  120. 120.
    Abraham EG, Islam S, Srinivasan P et al. Analysis of the Plasmodium and Anopheles transcriptional repertoire during ookinete development and midgut invasion. J Biol Chem 2004; 279:5573–5580.PubMedGoogle Scholar
  121. 121.
    Vlachou D, Schlegelmilch T, Christophides GK et al. Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion. Curr Biol 2005; 15:1185–1195.PubMedGoogle Scholar
  122. 122.
    Xu X, Dong Y, Abraham EG et al. Transcriptome analysis of Anopheles stephensi-Plasmodium berghei interactions. Mol Biochem Parasitol 2005; 142:76–87.PubMedGoogle Scholar
  123. 123.
    Gupta L, Kumar S, Han YS et al. Midgut epithelial responses of different mosquito-Plasmodium combinations: The actin cone zipper repair mechanism in Aedes aegypti. Proc Natl Acad Sci USA 2005; 102:4010–4015.PubMedGoogle Scholar
  124. 124.
    Kumar S, Gupta L, Han YS et al. Inducible peroxidases mediate nitration of anopheles midgut cells undergoing apoptosis in response to Plasmodium invasion. J Biol Chem 2004; 279:53475–53482.PubMedGoogle Scholar
  125. 125.
    Danielli A, Barillas-Mury C, Kumar S et al. Overexpression and altered nucleocytoplasmic distribution of Anopheles ovalbumin-like SRPN10 serpins in Plasmodium-infected midgut cells. Cell Microbiol 2005; 7:181–190.PubMedGoogle Scholar
  126. 126.
    Yuda M, Ishino T. Liver invasion by malaria parasites—how do malaria parasites break through the host barrier? Cell Microbiol 2004; 6:1119–1125.PubMedGoogle Scholar
  127. 127.
    Han YS, Barillas-Mury C. Implications of Time Bomb model of ookinete invasion of midgut cells. Insect Biochem Mol Biol 2002; 32:1311–1316.PubMedGoogle Scholar
  128. 128.
    Baton LA, Ranford-Cartwright LC. How do malaria ookinetes cross the mosquito midgut wall? Trends Parasitol 2005; 21:22–28.PubMedGoogle Scholar
  129. 129.
    Hurd H. Manipulation of medically important insect vectors by their parasites. Annu Rev Entomol 2003; 48:141–161.PubMedGoogle Scholar
  130. 130.
    Hurd H. Host fecundity reduction: a strategy for damage limitation? Trends Parasitol 2001; 17:363–368.PubMedGoogle Scholar
  131. 131.
    Hopwood JA, Ahmed AM, Polwart A et al. Malaria-induced apoptosis in mosquito ovaries: a mechanism to control vector egg production. J Exp Biol 2001; 204:2773–2780.PubMedGoogle Scholar
  132. 132.
    Ahmed AM, Hurd H. Immune stimulation and malaria infection impose reproductive costs in Anopheles gambiae via follicular apoptosis. Microbes Infect 2006; 8:308–315.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Luke A. Baton
    • 1
  • Emma Warr
    • 1
  • Seth A. Hoffman
    • 1
  • George Dimopoulos
    • 1
  1. 1.W. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreUSA

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