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Adaptive Immunity to Plasmodium Blood Stages

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Malaria

Chapter Summary

Adaptive immune responses to Plasmodium infection develop over many years in malaria-exposed individuals. Natural immunity is capable of reducing the severity of infection and lowering overall parasitemia but does not block infection. Moreover, there is some evidence that clinical immunity is short-lived as individuals who leave endemic areas become susceptible to disease once more. A proper understanding of the adaptive immune response is important to the pathology-causing blood-stage infection, not least because the induction of anti-disease immunity is one possible Plasmodium vaccination strategy. Nonetheless, the correlates of protective immunity are incompletely understood, and the reasons for the slow and incomplete development of immunity are unclear. Here we briefly review what is known about the roles of antibodies, B cells and T cells, in mediating protection. We examine which parasite antigens are likely to be the targets of protective antibodies. Finally we discuss why better, sterilizing, immunity to malaria does not develop with an emphasis on the fate of memory B and T cell populations in infection.

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References

  1. Gupta S, Snow RW, Donnelly CA, Marsh K, Newbold C (1999) Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med 5(3):340–343. doi:10.1038/6560

    Article  CAS  PubMed  Google Scholar 

  2. McGregor IA (1964) Studies in the acquisition of immunity of Plasmodium falciparum infections in Africa. Trans R Soc Trop Med Hyg 58:80–92

    Article  CAS  PubMed  Google Scholar 

  3. Snow RW, Nahlen B, Palmer A, Donnelly CA, Gupta S, Marsh K (1998) Risk of severe malaria among African infants: direct evidence of clinical protection during early infancy. J Infect Dis 177(3):819–822

    Article  CAS  PubMed  Google Scholar 

  4. Bouchaud O, Cot M, Kony S, Durand R, Schiemann R, Ralaimazava P, Coulaud JP, Le Bras J, Deloron P (2005) Do African immigrants living in France have long-term malarial immunity? Am J Trop Med Hyg 72(1):21–25

    PubMed  Google Scholar 

  5. Pistone T, Diallo A, Mechain M, Receveur MC, Malvy D (2014) Epidemiology of imported malaria give support to the hypothesis of ‘long-term’ semi-immunity to malaria in sub-Saharan African migrants living in France. Travel Med Infect Dis 12(1):48–53. doi:10.1016/j.tmaid.2013.08.006

    Article  CAS  PubMed  Google Scholar 

  6. Collins WE, Jeffery GM (1999) A retrospective examination of the patterns of recrudescence in patients infected with Plasmodium falciparum. Am J Trop Med Hyg 61(1 Suppl):44–48

    Article  CAS  PubMed  Google Scholar 

  7. Collins WE, Jeffery GM (1999) A retrospective examination of secondary sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity following secondary infection. Am J Trop Med Hyg 61(1 Suppl):20–35

    Article  CAS  PubMed  Google Scholar 

  8. Collins WE, Jeffery GM (1999) A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity during primary infection. Am J Trop Med Hyg 61(1 Suppl):4–19

    Article  CAS  PubMed  Google Scholar 

  9. Langhorne J, Ndungu FM, Sponaas AM, Marsh K (2008) Immunity to malaria: more questions than answers. Nat Immunol 9(7):725–732. doi:10.1038/ni.f.205

    Article  CAS  PubMed  Google Scholar 

  10. Tran TM, Li S, Doumbo S, Doumtabe D, Huang CY, Dia S, Bathily A, Sangala J, Kone Y, Traore A, Niangaly M, Dara C, Kayentao K, Ongoiba A, Doumbo OK, Traore B, Crompton PD (2013) An intensive longitudinal cohort study of Malian children and adults reveals no evidence of acquired immunity to Plasmodium falciparum infection. Clin Infect Dis 57(1):40–47. doi:10.1093/cid/cit174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Portugal S, Moebius J, Skinner J, Doumbo S, Doumtabe D, Kone Y, Dia S, Kanakabandi K, Sturdevant DE, Virtaneva K, Porcella SF, Li S, Doumbo OK, Kayentao K, Ongoiba A, Traore B, Crompton PD (2014) Exposure-dependent control of malaria-induced inflammation in children. PLoS Pathog 10(4), e1004079. doi:10.1371/journal.ppat.1004079

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sonden K, Doumbo S, Hammar U, Vafa Homann M, Ongoiba A, Traore B, Bottai M, Crompton PD, Farnert A (2015) Asymptomatic multiclonal Plasmodium falciparum infections carried through the dry season predict protection against subsequent clinical malaria. J Infect Dis 212(4):608–616. doi:10.1093/infdis/jiv088

    Article  PubMed  PubMed Central  Google Scholar 

  13. Brown IN, Brown KN, Hills LA (1968) Immunity to malaria: the antibody response to antigenic variation by Plasmodium knowlesi. Immunology 14(1):127–138

    CAS  PubMed  PubMed Central  Google Scholar 

  14. McLean SA, Pearson CD, Phillips RS (1982) Plasmodium chabaudi: antigenic variation during recrudescent parasitaemias in mice. Exp Parasitol 54(3):296–302

    Article  CAS  PubMed  Google Scholar 

  15. Cohen S, Mc GI, Carrington S (1961) Gamma-globulin and acquired immunity to human malaria. Nature 192:733–737

    Article  CAS  PubMed  Google Scholar 

  16. Bouharoun-Tayoun H, Attanath P, Sabchareon A, Chongsuphajaisiddhi T, Druilhe P (1990) Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J Exp Med 172(6):1633–1641

    Article  CAS  PubMed  Google Scholar 

  17. Sabchareon A, Burnouf T, Ouattara D, Attanath P, Bouharoun-Tayoun H, Chantavanich P, Foucault C, Chongsuphajaisiddhi T, Druilhe P (1991) Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg 45(3):297–308

    CAS  PubMed  Google Scholar 

  18. Hirunpetcharat C, Vukovic P, Liu XQ, Kaslow DC, Miller LH, Good MF (1999) Absolute requirement for an active immune response involving B cells and Th cells in immunity to Plasmodium yoelii passively acquired with antibodies to the 19-kDa carboxyl-terminal fragment of merozoite surface protein-1. J Immunol 162(12):7309–7314

    CAS  PubMed  Google Scholar 

  19. Meding SJ, Langhorne J (1991) CD4+ T cells and B cells are necessary for the transfer of protective immunity to Plasmodium chabaudi chabaudi. Eur J Immunol 21(6):1433–1438. doi:10.1002/eji.1830210616

    Article  CAS  PubMed  Google Scholar 

  20. Stephens R, Albano FR, Quin S, Pascal BJ, Harrison V, Stockinger B, Kioussis D, Weltzien HU, Langhorne J (2005) Malaria-specific transgenic CD4+ T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance. Blood 106(5):1676–1684. doi:10.1182/blood-2004-10-4047

    Article  CAS  PubMed  Google Scholar 

  21. Yap GS, Stevenson MM (1994) Differential requirements for an intact spleen in induction and expression of B-cell-dependent immunity to Plasmodium chabaudi AS. Infect Immun 62(10):4219–4225

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Dorfman JR, Bejon P, Ndungu FM, Langhorne J, Kortok MM, Lowe BS, Mwangi TW, Williams TN, Marsh K (2005) B cell memory to 3 Plasmodium falciparum blood-stage antigens in a malaria-endemic area. J Infect Dis 191(10):1623–1630. doi:10.1086/429671

    Article  CAS  PubMed  Google Scholar 

  23. Ndungu FM, Cadman ET, Coulcher J, Nduati E, Couper E, Macdonald DW, Ng D, Langhorne J (2009) Functional memory B cells and long-lived plasma cells are generated after a single Plasmodium chabaudi infection in mice. PLoS Pathog 5(12), e1000690. doi:10.1371/journal.ppat.1000690

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Ndungu FM, Lundblom K, Rono J, Illingworth J, Eriksson S, Farnert A (2013) Long-lived Plasmodium falciparum specific memory B cells in naturally exposed Swedish travelers. Eur J Immunol 43(11):2919–2929. doi:10.1002/eji.201343630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ndungu FM, Olotu A, Mwacharo J, Nyonda M, Apfeld J, Mramba LK, Fegan GW, Bejon P, Marsh K (2012) Memory B cells are a more reliable archive for historical antimalarial responses than plasma antibodies in no-longer exposed children. Proc Natl Acad Sci U S A 109(21):8247–8252. doi:10.1073/pnas.1200472109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wykes MN, Zhou YH, Liu XQ, Good MF (2005) Plasmodium yoelii can ablate vaccine-induced long-term protection in mice. J Immunol 175(4):2510–2516

    Article  CAS  PubMed  Google Scholar 

  27. Crompton PD, Miura K, Traore B, Kayentao K, Ongoiba A, Weiss G, Doumbo S, Doumtabe D, Kone Y, Huang CY, Doumbo OK, Miller LH, Long CA, Pierce SK (2010) In vitro growth-inhibitory activity and malaria risk in a cohort study in mali. Infect Immun 78(2):737–745. doi:10.1128/IAI.00960-09

    Article  CAS  PubMed  Google Scholar 

  28. Chan JA, Fowkes FJ, Beeson JG (2014) Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates. Cell Mol Life Sci 71(19):3633–3657. doi:10.1007/s00018-014-1614-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chiu CY, Healer J, Thompson JK, Chen L, Kaul A, Savergave L, Raghuwanshi A, Li Wai Suen CS, Siba PM, Schofield L, Mueller I, Cowman AF, Hansen DS (2014) Association of antibodies to Plasmodium falciparum reticulocyte binding protein homolog 5 with protection from clinical malaria. Front Microbiol 5:314. doi:10.3389/fmicb.2014.00314

    Article  PubMed  PubMed Central  Google Scholar 

  30. Fowkes FJ, Richards JS, Simpson JA, Beeson JG (2010) The relationship between anti-merozoite antibodies and incidence of Plasmodium falciparum malaria: a systematic review and meta-analysis. PLoS Med 7(1), e1000218. doi:10.1371/journal.pmed.1000218

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Tran TM, Ongoiba A, Coursen J, Crosnier C, Diouf A, Huang CY, Li S, Doumbo S, Doumtabe D, Kone Y, Bathily A, Dia S, Niangaly M, Dara C, Sangala J, Miller LH, Doumbo OK, Kayentao K, Long CA, Miura K, Wright GJ, Traore B, Crompton PD (2014) Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria. J Infect Dis 209(5):789–798. doi:10.1093/infdis/jit553

    Article  CAS  PubMed  Google Scholar 

  32. Lawton J, Brugat T, Yan YX, Reid AJ, Bohme U, Otto TD, Pain A, Jackson A, Berriman M, Cunningham D, Preiser P, Langhorne J (2012) Characterization and gene expression analysis of the cir multi-gene family of Plasmodium chabaudi chabaudi (AS). BMC Genomics 13:125. doi:10.1186/1471-2164-13-125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yam XY, Brugat T, Siau A, Lawton J, Wong DS, Farah A, Twang JS, Gao X, Langhorne J, Preiser PR (2016) Characterization of the Plasmodium interspersed repeats (PIR) proteins of Plasmodium chabaudi indicates functional diversity. Sci Rep 6:23449. doi:10.1038/srep23449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gilks CF, Walliker D, Newbold CI (1990) Relationships between sequestration, antigenic variation and chronic parasitism in Plasmodium chabaudi chabaudi—a rodent malaria model. Parasite Immunol 12(1):45–64

    Article  CAS  PubMed  Google Scholar 

  35. Bull PC, Lowe BS, Kortok M, Molyneux CS, Newbold CI, Marsh K (1998) Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat Med 4(3):358–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bull PC, Lowe BS, Kortok M, Marsh K (1999) Antibody recognition of Plasmodium falciparum erythrocyte surface antigens in Kenya: evidence for rare and prevalent variants. Infect Immun 67(2):733–739

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Voss TS, Healer J, Marty AJ, Duffy MF, Thompson JK, Beeson JG, Reeder JC, Crabb BS, Cowman AF (2006) A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria. Nature 439(7079):1004–1008. doi:10.1038/nature04407

    CAS  PubMed  Google Scholar 

  38. Chan JA, Howell KB, Reiling L, Ataide R, Mackintosh CL, Fowkes FJ, Petter M, Chesson JM, Langer C, Warimwe GM, Duffy MF, Rogerson SJ, Bull PC, Cowman AF, Marsh K, Beeson JG (2012) Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity. J Clin Invest 122(9):3227–3238. doi:10.1172/JCI62182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419(6906):498–511. doi:10.1038/nature01097

    Article  CAS  PubMed  Google Scholar 

  40. Kraemer SM, Smith JD (2003) Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family. Mol Microbiol 50(5):1527–1538

    Article  CAS  PubMed  Google Scholar 

  41. Jensen AT, Magistrado P, Sharp S, Joergensen L, Lavstsen T, Chiucchiuini A, Salanti A, Vestergaard LS, Lusingu JP, Hermsen R, Sauerwein R, Christensen J, Nielsen MA, Hviid L, Sutherland C, Staalsoe T, Theander TG (2004) Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. J Exp Med 199(9):1179–1190. doi:10.1084/jem.20040274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kaestli M, Cockburn IA, Cortes A, Baea K, Rowe JA, Beck HP (2006) Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a case–control study. J Infect Dis 193(11):1567–1574. doi:10.1086/503776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kyriacou HM, Stone GN, Challis RJ, Raza A, Lyke KE, Thera MA, Kone AK, Doumbo OK, Plowe CV, Rowe JA (2006) Differential var gene transcription in Plasmodium falciparum isolates from patients with cerebral malaria compared to hyperparasitaemia. Mol Biochem Parasitol 150(2):211–218. doi:10.1016/j.molbiopara.2006.08.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cham GK, Turner L, Kurtis JD, Mutabingwa T, Fried M, Jensen AT, Lavstsen T, Hviid L, Duffy PE, Theander TG (2010) Hierarchical, domain type-specific acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 in Tanzanian children. Infect Immun 78(11):4653–4659. doi:10.1128/IAI.00593-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cham GK, Turner L, Lusingu J, Vestergaard L, Mmbando BP, Kurtis JD, Jensen AT, Salanti A, Lavstsen T, Theander TG (2009) Sequential, ordered acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 domains. J Immunol 183(5):3356–3363. doi:10.4049/jimmunol.0901331

    Article  CAS  PubMed  Google Scholar 

  46. Abdel-Latif MS, Dietz K, Issifou S, Kremsner PG, Klinkert MQ (2003) Antibodies to Plasmodium falciparum rifin proteins are associated with rapid parasite clearance and asymptomatic infections. Infect Immun 71(11):6229–6233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tan J, Pieper K, Piccoli L, Abdi A, Foglierini M, Geiger R, Tully CM, Jarrossay D, Ndungu FM, Wambua J, Bejon P, Fregni CS, Fernandez-Rodriguez B, Barbieri S, Bianchi S, Marsh K, Thathy V, Corti D, Sallusto F, Bull P, Lanzavecchia A (2016) A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens. Nature 529(7584):105–109. doi:10.1038/nature16450

    Article  CAS  PubMed  Google Scholar 

  48. Blackman MJ, Scott-Finnigan TJ, Shai S, Holder AA (1994) Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein. J Exp Med 180(1):389–393

    Article  CAS  PubMed  Google Scholar 

  49. Kocken CH, Narum DL, Massougbodji A, Ayivi B, Dubbeld MA, van der Wel A, Conway DJ, Sanni A, Thomas AW (2000) Molecular characterisation of Plasmodium reichenowi apical membrane antigen-1 (AMA-1), comparison with P. falciparum AMA-1, and antibody-mediated inhibition of red cell invasion. Mol Biochem Parasitol 109(2):147–156

    Article  CAS  PubMed  Google Scholar 

  50. O’Donnell RA, de Koning-Ward TF, Burt RA, Bockarie M, Reeder JC, Cowman AF, Crabb BS (2001) Antibodies against merozoite surface protein (MSP)-119 are a major component of the invasion-inhibitory response in individuals immune to malaria. J Exp Med 193(12):1403–1412

    Article  PubMed  PubMed Central  Google Scholar 

  51. Irani V, Ramsland PA, Guy AJ, Siba PM, Mueller I, Richards JS, Beeson JG (2015) Acquisition of functional antibodies that block the binding of erythrocyte-binding antigen 175 and protection against Plasmodium falciparum malaria in children. Clin Infect Dis 61(8):1244–1252. doi:10.1093/cid/civ525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Persson KE, McCallum FJ, Reiling L, Lister NA, Stubbs J, Cowman AF, Marsh K, Beeson JG (2008) Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies. J Clin Invest 118(1):342–351. doi:10.1172/JCI32138

    Article  CAS  PubMed  Google Scholar 

  53. Crompton PD, Kayala MA, Traore B, Kayentao K, Ongoiba A, Weiss GE, Molina DM, Burk CR, Waisberg M, Jasinskas A, Tan X, Doumbo S, Doumtabe D, Kone Y, Narum DL, Liang X, Doumbo OK, Miller LH, Doolan DL, Baldi P, Felgner PL, Pierce SK (2010) A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Natl Acad Sci U S A 107(15):6958–6963. doi:10.1073/pnas.1001323107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Davies DH, Duffy P, Bodmer JL, Felgner PL, Doolan DL (2015) Large screen approaches to identify novel malaria vaccine candidates. Vaccine 33(52):7496–7505. doi:10.1016/j.vaccine.2015.09.059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Boyle MJ, Reiling L, Feng G, Langer C, Osier FH, Aspeling-Jones H, Cheng YS, Stubbs J, Tetteh KK, Conway DJ, McCarthy JS, Muller I, Marsh K, Anders RF, Beeson JG (2015) Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria. Immunity 42(3):580–590. doi:10.1016/j.immuni.2015.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kennedy AT, Schmidt CQ, Thompson JK, Weiss GE, Taechalertpaisarn T, Gilson PR, Barlow PN, Crabb BS, Cowman AF, Tham WH (2016) Recruitment of factor H as a novel complement evasion strategy for blood-stage Plasmodium falciparum infection. J Immunol 196(3):1239–1248. doi:10.4049/jimmunol.1501581

    Article  CAS  PubMed  Google Scholar 

  57. Rosa TF, Flammersfeld A, Ngwa CJ, Kiesow M, Fischer R, Zipfel PF, Skerka C, Pradel G (2016) The Plasmodium falciparum blood stages acquire factor H family proteins to evade destruction by human complement. Cell Microbiol 18(4):573–590. doi:10.1111/cmi.12535

    Article  CAS  PubMed  Google Scholar 

  58. Perez-Mazliah D, Ng DH, Freitas do Rosario AP, McLaughlin S, Mastelic-Gavillet B, Sodenkamp J, Kushinga G, Langhorne J (2015) Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria. PLoS Pathog 11(3), e1004715. doi:10.1371/journal.ppat.1004715

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Su Z, Stevenson MM (2002) IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice. J Immunol 168(3):1348–1355

    Article  CAS  PubMed  Google Scholar 

  60. Mota MM, Brown KN, Holder AA, Jarra W (1998) Acute Plasmodium chabaudi chabaudi malaria infection induces antibodies which bind to the surfaces of parasitized erythrocytes and promote their phagocytosis by macrophages in vitro. Infect Immun 66(9):4080–4086

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Langhorne J, Meding SJ, Eichmann K, Gillard SS (1989) The response of CD4+ T cells to Plasmodium chabaudi chabaudi. Immunol Rev 112:71–94

    Article  CAS  PubMed  Google Scholar 

  62. Podoba JE, Stevenson MM (1991) CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS. Infect Immun 59(1):51–58

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Stevenson MM, Tam MF (1993) Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin Exp Immunol 92(1):77–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. McCall MB, Sauerwein RW (2010) Interferon-gamma—central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria. J Leukoc Biol 88(6):1131–1143. doi:10.1189/jlb.0310137

    Article  CAS  PubMed  Google Scholar 

  65. Amante FH, Good MF (1997) Prolonged Th1-like response generated by a Plasmodium yoelii-specific T cell clone allows complete clearance of infection in reconstituted mice. Parasite Immunol 19(3):111–126

    Article  CAS  PubMed  Google Scholar 

  66. Muxel SM, Freitas do Rosario AP, Zago CA, Castillo-Mendez SI, Sardinha LR, Rodriguez-Malaga SM, Camara NO, Alvarez JM, Lima MR (2011) The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. PLoS One 6(7), e22434. doi:10.1371/journal.pone.0022434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Jacobs P, Radzioch D, Stevenson MM (1996) In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon, but not by interleukin-4, during blood stage malaria in mice. Infect Immun 64(1):44–49

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Stephens R, Langhorne J (2010) Effector memory Th1 CD4 T cells are maintained in a mouse model of chronic malaria. PLoS Pathog 6(11), e1001208. doi:10.1371/journal.ppat.1001208

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Opata MM, Carpio VH, Ibitokou SA, Dillon BE, Obiero JM, Stephens R (2015) Early effector cells survive the contraction phase in malaria infection and generate both central and effector memory T cells. J Immunol 194(11):5346–5354. doi:10.4049/jimmunol.1403216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Achtman AH, Stephens R, Cadman ET, Harrison V, Langhorne J (2007) Malaria-specific antibody responses and parasite persistence after infection of mice with Plasmodium chabaudi chabaudi. Parasite Immunol 29(9):435–444. doi:10.1111/j.1365-3024.2007.00960.x

    Article  CAS  PubMed  Google Scholar 

  71. Perignon JL, Druilhe P (1994) Immune mechanisms underlying the premunition against Plasmodium falciparum malaria. Mem Inst Oswaldo Cruz 89(Suppl 2):51–53

    Article  PubMed  Google Scholar 

  72. Roetynck S, Olotu A, Simam J, Marsh K, Stockinger B, Urban B, Langhorne J (2013) Phenotypic and functional profiling of CD4 T cell compartment in distinct populations of healthy adults with different antigenic exposure. PLoS One 8(1), e55195. doi:10.1371/journal.pone.0055195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mewono L, Matondo Maya DW, Matsiegui PB, Agnandji ST, Kendjo E, Barondi F, Issifou S, Kremsner PG, Mavoungou E (2008) Interleukin-21 is associated with IgG1 and IgG3 antibodies to erythrocyte-binding antigen-175 peptide 4 of Plasmodium falciparum in Gabonese children with acute falciparum malaria. Eur Cytokine Netw 19(1):30–36. doi:10.1684/ecn.2008.0114

    CAS  PubMed  Google Scholar 

  74. Pombo DJ, Lawrence G, Hirunpetcharat C, Rzepczyk C, Bryden M, Cloonan N, Anderson K, Mahakunkijcharoen Y, Martin LB, Wilson D, Elliott S, Elliott S, Eisen DP, Weinberg JB, Saul A, Good MF (2002) Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet 360(9333):610–617. doi:10.1016/S0140-6736(02)09784-2

    Article  PubMed  Google Scholar 

  75. Edstein MD, Kotecka BM, Anderson KL, Pombo DJ, Kyle DE, Rieckmann KH, Good MF (2005) Lengthy antimalarial activity of atovaquone in human plasma following atovaquone-proguanil administration. Antimicrob Agents Chemother 49(10):4421–4422. doi:10.1128/AAC.49.10.4421-4422.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R (2009) Protection against a malaria challenge by sporozoite inoculation. N Engl J Med 361(5):468–477. doi:10.1056/NEJMoa0805832

    Article  CAS  PubMed  Google Scholar 

  77. Bijker EM, Bastiaens GJ, Teirlinck AC, van Gemert GJ, Graumans W, van de Vegte-Bolmer M, Siebelink-Stoter R, Arens T, Teelen K, Nahrendorf W, Remarque EJ, Roeffen W, Jansens A, Zimmerman D, Vos M, van Schaijk BC, Wiersma J, van der Ven AJ, de Mast Q, van Lieshout L, Verweij JJ, Hermsen CC, Scholzen A, Sauerwein RW (2013) Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity. Proc Natl Acad Sci U S A 110(19):7862–7867. doi:10.1073/pnas.1220360110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Luty AJ, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Migot-Nabias F, Deloron P, Nussenzweig RS, Kremsner PG (1999) Interferon-gamma responses are associated with resistance to reinfection with Plasmodium falciparum in young African children. J Infect Dis 179(4):980–988. doi:10.1086/314689

    Article  CAS  PubMed  Google Scholar 

  79. Jagannathan P, Eccles-James I, Bowen K, Nankya F, Auma A, Wamala S, Ebusu C, Muhindo MK, Arinaitwe E, Briggs J, Greenhouse B, Tappero JW, Kamya MR, Dorsey G, Feeney ME (2014) IFNgamma/IL-10 co-producing cells dominate the CD4 response to malaria in highly exposed children. PLoS Pathog 10(1), e1003864. doi:10.1371/journal.ppat.1003864

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Jagannathan P, Nankya F, Stoyanov C, Eccles-James I, Sikyomu E, Naluwu K, Wamala S, Nalubega M, Briggs J, Bowen K, Bigira V, Kapisi J, Kamya MR, Dorsey G, Feeney ME (2015) IFNgamma responses to pre-erythrocytic and blood-stage malaria antigens exhibit differential associations with past exposure and subsequent protection. J Infect Dis 211(12):1987–1996. doi:10.1093/infdis/jiu814

    Article  CAS  PubMed  Google Scholar 

  81. Boyle MJ, Jagannathan P, Bowen K, McIntyre TI, Vance HM, Farrington LA, Greenhouse B, Nankya F, Rek J, Katureebe A, Arinaitwe E, Dorsey G, Kamya MR, Feeney ME (2015) Effector phenotype of Plasmodium falciparum-specific CD4+ T cells is influenced by both age and transmission intensity in naturally exposed populations. J Infect Dis 212(3):416–425. doi:10.1093/infdis/jiv054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Beattie L, Engwerda CR, Wykes M, Good MF (2006) CD8+ T lymphocyte-mediated loss of marginal metallophilic macrophages following infection with Plasmodium chabaudi chabaudi AS. J Immunol 177(4):2518–2526

    Article  CAS  PubMed  Google Scholar 

  83. Hafalla JC, Cockburn IA, Zavala F (2006) Protective and pathogenic roles of CD8+ T cells during malaria infection. Parasite Immunol 28(1–2):15–24. doi:10.1111/j.1365-3024.2006.00777.x

    Article  CAS  PubMed  Google Scholar 

  84. Suss G, Eichmann K, Kury E, Linke A, Langhorne J (1988) Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi. Infect Immun 56(12):3081–3088

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Imai T, Shen J, Chou B, Duan X, Tu L, Tetsutani K, Moriya C, Ishida H, Hamano S, Shimokawa C, Hisaeda H, Himeno K (2010) Involvement of CD8+ T cells in protective immunity against murine blood-stage infection with Plasmodium yoelii 17XL strain. Eur J Immunol 40(4):1053–1061. doi:10.1002/eji.200939525

    Article  CAS  PubMed  Google Scholar 

  86. Imai T, Ishida H, Suzue K, Hirai M, Taniguchi T, Okada H, Suzuki T, Shimokawa C, Hisaeda H (2013) CD8+ T cell activation by murine erythroblasts infected with malaria parasites. Sci Rep 3:1572. doi:10.1038/srep01572

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Safeukui I, Gomez ND, Adelani AA, Burte F, Afolabi NK, Akondy R, Velazquez P, Holder A, Tewari R, Buffet P, Brown BJ, Shokunbi WA, Olaleye D, Sodeinde O, Kazura J, Ahmed R, Mohandas N, Fernandez-Reyes D, Haldar K (2015) Malaria induces anemia through CD8+ T cell-dependent parasite clearance and erythrocyte removal in the spleen. MBio 6(1), e02493-14. doi:10.1128/mBio.02493-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Horne-Debets JM, Faleiro R, Karunarathne DS, Liu XQ, Lineburg KE, Poh CM, Grotenbreg GM, Hill GR, MacDonald KP, Good MF, Renia L, Ahmed R, Sharpe AH, Wykes MN (2013) PD-1 dependent exhaustion of CD8+ T cells drives chronic malaria. Cell Rep 5(5):1204–1213. doi:10.1016/j.celrep.2013.11.002

    Article  CAS  PubMed  Google Scholar 

  89. Cockburn IA, Zavala F (2016) Dendritic cell function and antigen presentation in malaria. Curr Opin Immunol 40:1–6. doi:10.1016/j.coi.2016.01.010

    Article  CAS  PubMed  Google Scholar 

  90. Wykes MN, Good MF (2008) What really happens to dendritic cells during malaria? Nat Rev Microbiol 6(11):864–870. doi:10.1038/nrmicro1988

    CAS  PubMed  Google Scholar 

  91. Walther M, Tongren JE, Andrews L, Korbel D, King E, Fletcher H, Andersen RF, Bejon P, Thompson F, Dunachie SJ, Edele F, de Souza JB, Sinden RE, Gilbert SC, Riley EM, Hill AV (2005) Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity 23(3):287–296. doi:10.1016/j.immuni.2005.08.006

    Article  CAS  PubMed  Google Scholar 

  92. Minigo G, Woodberry T, Piera KA, Salwati E, Tjitra E, Kenangalem E, Price RN, Engwerda CR, Anstey NM, Plebanski M (2009) Parasite-dependent expansion of TNF receptor II-positive regulatory T cells with enhanced suppressive activity in adults with severe malaria. PLoS Pathog 5(4), e1000402. doi:10.1371/journal.ppat.1000402

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Illingworth J, Butler NS, Roetynck S, Mwacharo J, Pierce SK, Bejon P, Crompton PD, Marsh K, Ndungu FM (2013) Chronic exposure to Plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion. J Immunol 190(3):1038–1047. doi:10.4049/jimmunol.1202438

    Article  CAS  PubMed  Google Scholar 

  94. Weiss GE, Crompton PD, Li S, Walsh LA, Moir S, Traore B, Kayentao K, Ongoiba A, Doumbo OK, Pierce SK (2009) Atypical memory B cells are greatly expanded in individuals living in a malaria-endemic area. J Immunol 183(3):2176–2182. doi:10.4049/jimmunol.0901297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Portugal S, Tipton CM, Sohn H, Kone Y, Wang J, Li S, Skinner J, Virtaneva K, Sturdevant DE, Porcella SF, Doumbo OK, Doumbo S, Kayentao K, Ongoiba A, Traore B, Sanz I, Pierce SK, Crompton PD (2015) Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function. Elife 4, e07218. doi:10.7554/eLife.07218

    Article  PubMed Central  CAS  Google Scholar 

  96. Sullivan RT, Kim CC, Fontana MF, Feeney ME, Jagannathan P, Boyle MJ, Drakeley CJ, Ssewanyana I, Nankya F, Mayanja-Kizza H, Dorsey G, Greenhouse B (2015) FCRL5 delineates functionally impaired memory B cells associated with Plasmodium falciparum exposure. PLoS Pathog 11(5), e1004894. doi:10.1371/journal.ppat.1004894

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Dauby N, Kummert C, Lecomte S, Liesnard C, Delforge ML, Donner C, Marchant A (2014) Primary human cytomegalovirus infection induces the expansion of virus-specific activated and atypical memory B cells. J Infect Dis 210(8):1275–1285. doi:10.1093/infdis/jiu255

    Article  CAS  PubMed  Google Scholar 

  98. Doi H, Tanoue S, Kaplan DE (2014) Peripheral CD27-CD21- B-cells represent an exhausted lymphocyte population in hepatitis C cirrhosis. Clin Immunol 150(2):184–191. doi:10.1016/j.clim.2013.12.001

    Article  CAS  PubMed  Google Scholar 

  99. Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, O’Shea MA, Roby G, Kottilil S, Arthos J, Proschan MA, Chun TW, Fauci AS (2008) Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med 205(8):1797–1805. doi:10.1084/jem.20072683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Muellenbeck MF, Ueberheide B, Amulic B, Epp A, Fenyo D, Busse CE, Esen M, Theisen M, Mordmuller B, Wardemann H (2013) Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies. J Exp Med 210(2):389–399. doi:10.1084/jem.20121970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Achtman AH, Bull PC, Stephens R, Langhorne J (2005) Longevity of the immune response and memory to blood-stage malaria infection. Curr Top Microbiol Immunol 297:71–102

    CAS  PubMed  Google Scholar 

  102. Weiss GE, Traore B, Kayentao K, Ongoiba A, Doumbo S, Doumtabe D, Kone Y, Dia S, Guindo A, Traore A, Huang CY, Miura K, Mircetic M, Li S, Baughman A, Narum DL, Miller LH, Doumbo OK, Pierce SK, Crompton PD (2010) The Plasmodium falciparum-specific human memory B cell compartment expands gradually with repeated malaria infections. PLoS Pathog 6(5), e1000912. doi:10.1371/journal.ppat.1000912

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Achtman AH, Khan M, MacLennan IC, Langhorne J (2003) Plasmodium chabaudi chabaudi infection in mice induces strong B cell responses and striking but temporary changes in splenic cell distribution. J Immunol 171(1):317–324

    Article  CAS  PubMed  Google Scholar 

  104. Urban BC, Hien TT, Day NP, Phu NH, Roberts R, Pongponratn E, Jones M, Mai NT, Bethell D, Turner GD, Ferguson D, White NJ, Roberts DJ (2005) Fatal Plasmodium falciparum malaria causes specific patterns of splenic architectural disorganization. Infect Immun 73(4):1986–1994. doi:10.1128/IAI.73.4.1986-1994.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Stephens R, Ndungu FM, Langhorne J (2009) Germinal centre and marginal zone B cells expand quickly in a second Plasmodium chabaudi malaria infection producing mature plasma cells. Parasite Immunol 31(1):20–31. doi:10.1111/j.1365-3024.2008.01066.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Portugal S, Pierce SK, Crompton PD (2013) Young lives lost as B cells falter: what we are learning about antibody responses in malaria. J Immunol 190(7):3039–3046. doi:10.4049/jimmunol.1203067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Carpio VH, Opata MM, Montanez ME, Banerjee PP, Dent AL, Stephens R (2015) IFN-gamma and IL-21 double producing T cells are Bcl6-independent and survive into the memory phase in Plasmodium chabaudi infection. PLoS One 10(12), e0144654. doi:10.1371/journal.pone.0144654

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Ryg-Cornejo V, Ioannidis LJ, Ly A, Chiu CY, Tellier J, Hill DL, Preston SP, Pellegrini M, Yu D, Nutt SL, Kallies A, Hansen DS (2016) Severe malaria infections impair germinal center responses by inhibiting T follicular helper cell differentiation. Cell Rep 14(1):68–81. doi:10.1016/j.celrep.2015.12.006

    Article  CAS  PubMed  Google Scholar 

  109. Zander RA, Obeng-Adjei N, Guthmiller JJ, Kulu DI, Li J, Ongoiba A, Traore B, Crompton PD, Butler NS (2015) PD-1 co-inhibitory and OX40 co-stimulatory crosstalk regulates helper T cell differentiation and anti-Plasmodium humoral immunity. Cell Host Microbe 17(5):628–641. doi:10.1016/j.chom.2015.03.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Wikenheiser DJ, Ghosh D, Kennedy B, Stumhofer JS (2016) The costimulatory molecule ICOS regulates host Th1 and follicular Th cell differentiation in response to Plasmodium chabaudi chabaudi AS infection. J Immunol 196(2):778–791. doi:10.4049/jimmunol.1403206

    Article  CAS  PubMed  Google Scholar 

  111. Obeng-Adjei N, Portugal S, Tran TM, Yazew TB, Skinner J, Li S, Jain A, Felgner PL, Doumbo OK, Kayentao K, Ongoiba A, Traore B, Crompton PD (2015) Circulating Th1-cell-type Tfh cells that exhibit impaired B cell help are preferentially activated during acute malaria in children. Cell Rep 13(2):425–439. doi:10.1016/j.celrep.2015.09.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H (2011) Human blood CXCR5+CD4+ T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34(1):108–121. doi:10.1016/j.immuni.2010.12.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Chelimo K, Sumba PO, Kazura JW, Ofula AV, John CC (2003) Interferon-gamma responses to Plasmodium falciparum liver-stage antigen-1 and merozoite-surface protein-1 increase with age in children in a malaria holoendemic area of western Kenya. Malar J 2(1):37. doi:10.1186/1475-2875-2-37

    Article  PubMed  PubMed Central  Google Scholar 

  114. Dent AE, Chelimo K, Sumba PO, Spring MD, Crabb BS, Moormann AM, Tisch DJ, Kazura JW (2009) Temporal stability of naturally acquired immunity to Merozoite Surface Protein-1 in Kenyan adults. Malar J 8:162. doi:10.1186/1475-2875-8-162

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Bixby LM, Tarleton RL (2008) Stable CD8+ T cell memory during persistent Trypanosoma cruzi infection. J Immunol 181(4):2644–2650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Colpitts SL, Dalton NM, Scott P (2009) IL-7 receptor expression provides the potential for long-term survival of both CD62Lhigh central memory T cells and Th1 effector cells during Leishmania major infection. J Immunol 182(9):5702–5711. doi:10.4049/jimmunol.0803450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Martin DL, Tarleton RL (2005) Antigen-specific T cells maintain an effector memory phenotype during persistent Trypanosoma cruzi infection. J Immunol 174(3):1594–1601

    Article  CAS  PubMed  Google Scholar 

  118. Zaph C, Uzonna J, Beverley SM, Scott P (2004) Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites. Nat Med 10(10):1104–1110. doi:10.1038/nm1108

    Article  CAS  PubMed  Google Scholar 

  119. Peters NC, Pagan AJ, Lawyer PG, Hand TW, Henrique Roma E, Stamper LW, Romano A, Sacks DL (2014) Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection. PLoS Pathog 10(12), e1004538. doi:10.1371/journal.ppat.1004538

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Freitas do Rosario AP, Muxel SM, Rodriguez-Malaga SM, Sardinha LR, Zago CA, Castillo-Mendez SI, Alvarez JM, D’Imperio Lima MR (2008) Gradual decline in malaria-specific memory T cell responses leads to failure to maintain long-term protective immunity to Plasmodium chabaudi AS despite persistence of B cell memory and circulating antibody. J Immunol 181(12):8344–8355

    Article  CAS  PubMed  Google Scholar 

  121. Wipasa J, Okell L, Sakkhachornphop S, Suphavilai C, Chawansuntati K, Liewsaree W, Hafalla JC, Riley EM (2011) Short-lived IFN-gamma effector responses, but long-lived IL-10 memory responses, to malaria in an area of low malaria endemicity. PLoS Pathog 7(2), e1001281. doi:10.1371/journal.ppat.1001281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Dong H, Zhu G, Tamada K, Chen L (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5(12):1365–1369. doi:10.1038/70932

    Article  CAS  PubMed  Google Scholar 

  123. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ (2001) PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2(3):261–268. doi:10.1038/85330

    Article  CAS  PubMed  Google Scholar 

  125. Tseng SY, Otsuji M, Gorski K, Huang X, Slansky JE, Pai SI, Shalabi A, Shin T, Pardoll DM, Tsuchiya H (2001) B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med 193(7):839–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ (2007) The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol 8(3):239–245. doi:10.1038/ni1443

    Article  CAS  PubMed  Google Scholar 

  127. Chandele A, Mukerjee P, Das G, Ahmed R, Chauhan VS (2011) Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii. Immunology 132(2):273–286. doi:10.1111/j.1365-2567.2010.03363.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Stephens R, Seddon B, Langhorne J (2011) Homeostatic proliferation and IL-7R alpha expression do not correlate with enhanced T cell proliferation and protection in chronic mouse malaria. PLoS One 6(10), e26686. doi:10.1371/journal.pone.0026686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Butler NS, Moebius J, Pewe LL, Traore B, Doumbo OK, Tygrett LT, Waldschmidt TJ, Crompton PD, Harty JT (2012) Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection. Nat Immunol 13(2):188–195. doi:10.1038/ni.2180

    Article  CAS  Google Scholar 

  130. Rts SCTP (2015) Efficacy and safety of RTS, S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet 386(9988):31–45. doi:10.1016/S0140-6736(15)60721-8

    Article  CAS  Google Scholar 

  131. Rts SCTP, Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG, Kabwende AL, Adegnika AA, Mordmuller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Machevo S, Acacio S, Bulo H, Sigauque B, Macete E, Alonso P, Abdulla S, Salim N, Minja R, Mpina M, Ahmed S, Ali AM, Mtoro AT, Hamad AS, Mutani P, Tanner M, Tinto H, D’Alessandro U, Sorgho H, Valea I, Bihoun B, Guiraud I, Kabore B, Sombie O, Guiguemde RT, Ouedraogo JB, Hamel MJ, Kariuki S, Oneko M, Odero C, Otieno K, Awino N, McMorrow M, Muturi-Kioi V, Laserson KF, Slutsker L, Otieno W, Otieno L, Otsyula N, Gondi S, Otieno A, Owira V, Oguk E, Odongo G, Woods JB, Ogutu B, Njuguna P, Chilengi R, Akoo P, Kerubo C, Maingi C, Lang T, Olotu A, Bejon P, Marsh K, Mwambingu G, Owusu-Agyei S, Asante KP, Osei-Kwakye K, Boahen O, Dosoo D, Asante I, Adjei G, Kwara E, Chandramohan D, Greenwood B, Lusingu J, Gesase S, Malabeja A, Abdul O, Mahende C, Liheluka E, Malle L, Lemnge M, Theander TG, Drakeley C, Ansong D, Agbenyega T, Adjei S, Boateng HO, Rettig T, Bawa J, Sylverken J, Sambian D, Sarfo A, Agyekum A, Martinson F, Hoffman I, Mvalo T, Kamthunzi P, Nkomo R, Tembo T, Tegha G, Tsidya M, Kilembe J, Chawinga C, Ballou WR, Cohen J, Guerra Y, Jongert E, Lapierre D, Leach A, Lievens M, Ofori-Anyinam O, Olivier A, Vekemans J, Carter T, Kaslow D, Leboulleux D, Loucq C, Radford A, Savarese B, Schellenberg D, Sillman M, Vansadia P (2012) A phase 3 trial of RTS, S/AS01 malaria vaccine in African infants. N Engl J Med 367(24):2284–2295. doi:10.1056/NEJMoa1208394

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4029, Australia

    Michelle N. Wykes

  2. Division of Infectious Diseases, Departments of Internal Medicine and Microbiology and Immunology, University of Texas Medical Branch, 301 University Drive, Galveston, TX, 77555-0435, USA

    Robin Stephens

  3. Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia

    Ian A. Cockburn

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  1. Michelle N. Wykes
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  1. Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal

    Maria M. Mota

  2. Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA

    Ana Rodriguez

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Wykes, M.N., Stephens, R., Cockburn, I.A. (2017). Adaptive Immunity to Plasmodium Blood Stages. In: Mota, M., Rodriguez, A. (eds) Malaria. Springer, Cham. https://doi.org/10.1007/978-3-319-45210-4_3

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