CD4 T-cell subsets in malaria: Th1/Th2 revisited

Frontiers in Immunology

Volumn 5, Issue DEC, 2014, Pages

  Perez Mazliah, Damian ^a   Langhorne, Jean ^a  

^a NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

Author keywords

CD4 T cell subsets; Malaria; Multifunctional CD4 T cells; Plasmodium; Tfh; Th1; Th2; Th22

Indexed keywords

EID: 84920105352     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00671     Document Type: Short Survey

References (98)

1. World Health Organization (2013). World Malaria Report.
2. Landau I. (1978). "Life cycles and morphology" in Rodent Malaria, ed. R Killick-Kendrick, Peters W (Academic Press), 53-84.
3. Stephens R, Culleton RL, and Lamb TJ. The contribution of Plasmodium chabaudi to our understanding of malaria. Trends Parasitol (2012) 28(2):73-82 doi: 10.1016/j.pt.2011.10.006.
4. Lamb TJ, Brown DE, Potocnik AJ, and Langhorne J. Insights into the immunopathogenesis of malaria using mouse models. Expert Rev Mol Med (2006) 8(06). doi: http://dx.doi.org/10.1017/S1462399406010581.
5. Schofield L. Intravascular infiltrates and organ-specific inflammation in malaria pathogenesis. Immunol Cell Biol (2007) 85(2):130-7. doi:10.1038/sj.icb.7100040.
6. Rénia L, Grillot D, Marussig M, Corradin G, Miltgen F, Lambert PH, et al. Effector functions of circumsporozoite peptide-primed CD4+ T cell clones against Plasmodium yoelii liver stage. J Immunol (1993) 150(4):1471-8.
7. Takita-Sonoda Y, Tsuji M, Kamboj K, Nussenzweig RS, Clavijo P, and Zavala F. Plasmodium yoelii: peptide immunization induces protective CD4+ T cells against a previously unrecognized cryptic epitope of the circumsporozoite protein. Exp Parasitol (1996) 84(2):223-30. doi: 10.1006/expr.1996.0108.
8. Carvalho LH, Sano G-I, Hafalla JCR, Morrot A, Curotto de Lafaille MA, and Zavala F. IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages. Nat Med (2002) 8(2):166-70. doi:10.1038/nm0202-166.
9. Oliveira GA, Kumar KA, Calvo-Calle JM, Othoro C, Altszuler D, Nussenzweig V, et al. Class II-restricted protective immunity induced by malaria sporozoites. Infect Immun (2008) 76(3):1200-6 doi:10.1128/IAI.00566-07.
10. Overstreet MG, Chen Y-C, Cockburn IA, Tse S-W, and Zavala F. CD4+ T cells modulate expansion and survival but not functional properties of effector and memory CD8+ T cells induced by malaria sporozoites. PloS One (2011) 6(1):e15948. doi: 10.1371/journal.pone.0015948.
11. Bijker EM, Teirlinck AC, Schats R, van Gemert G-J, van de Vegte-Bolmer M, van Lieshout L, et al. Cytotoxic Markers Associate With Protection Against Malaria in Human Volunteers Immunized With Plasmodium falciparum Sporozoites. J Infect Dis (2014) [Epub ahead of print] doi: 10.1093/infdis/jiu293.
12. Crompton PD, Kayala MA, Traore B, Kayentao K, Ongoiba A, Weiss GE, et al. A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray. Proc Nat Acad Sci USA (2010) 107(15):6958-63. doi: 10.1073/pnas.1001323107.
13. Felgner PL, Roestenberg M, Liang L, Hung C, Jain A, Pablo J, et al. Pre erythrocytic antibody profiles induced by controlled human malaria infections in healthy volunteers under chloroquine prophylaxis. Sci Rep (2013) 3:3549. doi: 10.1038/srep03549.
14. Nahrendorf W, Scholzen A, Bijker EM, Teirlinck AC, Bastiaens GJH, Schats R, et al. Memory B-Cell and Antibody Responses Induced by Plasmodium falciparum Sporozoite Immunization. J Infect Dis (2014) [Epub ahead of print] doi: 10.1093/infdis/jiu354.
15. Reece WHH, Pinder M, Gothard PK, Milligan P, Bojang K, Doherty T, et al. A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease. Nat Med (2004) 10(4):406-10. doi:10.1038/nm1009.
16. Chakravarty S, Cockburn IA, Kuk S, Overstreet MG, Sacci JB, Zavala F. CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. Nat Med (2007) 13(9):1035-41. doi: 10.1038/nm1628.
17. Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol (2011) 29:621-63. doi: 10.1146/annurev-immunol-031210-101400.
18. Mosmann TR, and Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol (1989) 7:145-73. doi: 10.1146/annurev.iy.07.040189.001045.
19. Huang KY, Schultz WW, and Gordon FB. Interferon induced by Plasmodium berghei. Science (1968) 162(3849):123-4. doi:10.1126/science.162.3849.123.
20. Troye-Blomberg M, Andersson G, Stoczkowska M, Shabo R, Romero P, Patarroyo ME, et al. Production of IL 2 and IFN-gamma by T cells from malaria patients in response to Plasmodium falciparum or erythrocyte antigens in vitro. J Immunol (1985) 135(5):3498-504.
21. Langhorne J, Gillard S, Simon B, Slade S, and Eichmann K. Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. Int Immunol (1989) 1(4):416-24.
22. Shear HL, Srinivasan R, Nolan T, and Ng C. Role of IFN-gamma in lethal and nonlethal malaria in susceptible and resistant murine hosts. J Immunol (1989) 143(6):2038-44.
23. Troye-Blomberg M, Riley EM, Perlmann H, Andersson G, Larsson A, Snow RW, et al. T and B cell responses of Plasmodium falciparum malaria-immune individuals to synthetic peptides corresponding to sequences in different regions of the P. falciparum antigen Pf155/RESA. J Immunol (1989) 143(9):3043-8.
24. Stevenson MM, and Tam MF. Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin Exp Immunol (1993) 92(1):77-83.
25. + T-cell lineage: when, how and what for? Open Biol (2013) 3(1):120157. doi: 10.1098/rsob.120157.
26. Lundie RJ, de Koning-Ward TF, Davey GM, Nie CQ, Hansen DS, Lau LS, et al. 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 (2008) 105(38):14509-14. doi: 10.1073/pnas.0806727105.
27. Sponaas AM, Cadman ET, Voisine C, Harrison V, Boonstra A, O'Garra A, et al. Malaria infection changes the ability of splenic dendritic cell populations to stimulate antigen-specific T cells. J Exp Med (2006) 203(6):1427-33. doi: 10.1084/jem.20052450.
28. deWalick S, Amante FH, McSweeney KA, Randall LM, Stanley AC, Haque A, et al. Cutting edge: conventional dendritic cells are the critical APC required for the induction of experimental cerebral malaria. J Immunol (2007) 178(10):6033-7.
29. Voisine C, Mastelic B, Sponaas A-M, Langhorne J. Classical CD11c+ dendritic cells, not plasmacytoid dendritic cells, induce T cell responses to Plasmodium chabaudi malaria. Int J Parasitol (2010) 40(6):711-9. doi: 10.1016/j.ijpara.2009.11.005.
30. Su Z, Stevenson MM. IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice. J Immunol (2002) 168(3):1348-55.
31. Sauvaget F, and Fauconnier B. The protective effect of endogenous interferon in mouse malaria, as demonstrated by the use of anti-interferon globulins. Biomedicine (1978) 29(6):184-7.
32. Meding SJ, Cheng SC, Simon-Haarhaus B, and Langhorne J. Role of gamma interferon during infection with Plasmodium chabaudi chabaudi. Infect Immun (1990) 58(11):3671-8.
33. Simon-Haarhaus B, Langhorne J, and Meding S. CD4+T cell-dependent effector mechanisms important in the immune response to the erythrocytic stages of Plasmodium chabaudi chabaudi (AS). Behring Inst Mitt (1991) (88):94-8.
34. Su Z, and Stevenson MM. Central role of endogenous gamma interferon in protective immunity against blood-stage Plasmodium chabaudi AS infection. Infect Immun (2000) 68(8):4399-406. doi: 10.1128/IAI.68.8.4399-4406.2000.
35. Stephens R, Langhorne J. Effector memory Th1 CD4 T cells are maintained in a mouse model of chronic malaria. PloS Pathog (2010) 6(11):e1001208. doi: 10.1371/journal.ppat.1001208.
36. da Silva HB, de Salles EM, Panatieri RH, Boscardin SB, Rodriguez-Málaga SM, álvarez JM, et al. IFN-?-induced priming maintains long-term strain transcending immunity against blood-stage Plasmodium chabaudi malaria. J Immunol (2013) 191(10):5160-9. doi: 10.4049/jimmunol.1300462.
37. McCall MBB, Sauerwein RW. Interferon-?-central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria. J Leukoc Biol (2010) 88(6):1131-43. doi: 10.1189/jlb.0310137.
38. Villegas-Mendez A, Greig R, Shaw TN, De Souza JB, Gwyer Findlay E, Stumhofer JS, et al. IFN-?-Producing CD4+ T Cells Promote Experimental Cerebral Malaria by Modulating CD8+ T Cell Accumulation within the Brain. J Immunol (2012) 189(2):968-79. doi: 10.4049/jimmunol.1200688.
39. + T-cell-dependent parasite control during blood-stage Plasmodium infection. Eur J Immunol (2011) 41(9):2688-98 doi: 10.1002/eji.201141539.
40. Haque A, Best SE, Montes de Oca M, James KR, Ammerdorffer A, Edwards CL, et al. Type I IFN signaling in CD8-DCs impairs Th1-dependent malaria immunity. J Clin Invest (2014) 124(6):2483-96. doi: 10.1172/JCI70698.
41. Oakley MS, Sahu BR, Lotspeich-Cole L, Solanki NR, Majam V, Pham PT, et al. The transcription factor T-bet regulates parasitemia and promotes pathogenesis during Plasmodium berghei ANKA murine malaria. J Immunol (2013) 191(9):4699-708. doi: 10.4049/jimmunol.1300396.
42. Chandele A, Mukerjee P, Das G, Ahmed R, Chauhan VS. Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood stage infection with Plasmodium yoelii. Immunology (2011) 132(2):273-86. doi: 10.1111/j.1365-2567.2010.03363.x.
43. Oakley MS, Sahu BR, Lotspeich-Cole L, Majam V, Thao Pham P, Sengupta Banerjee A, et al. T-bet modulates the antibody response and immune protection during murine malaria. Eur J Immunol (2014) 44(9):2680-91. doi: 10.1002/eji.201344437.
44. Troye-Blomberg M, Riley EM, Kabilan L, Holmberg M, Perlmann H, Andersson U, et al. Production by activated human T cells of interleukin 4 but not interferon-gamma is associated with elevated levels of serum antibodies to activating malaria antigens. Proc Nat Acad Sci USA (1990) 87(14):5484-8.
45. von der Weid T, Kopf M, Köhler G, and Langhorne J. The immune response to Plasmodium chabaudi malaria in interleukin-4-deficient mice. Eur J Immunol (1994) 24(10):2285-93. doi: 10.1002/eji.1830241004.
46. Linke A, Kühn R, Müller W, Honarvar N, Li C, and Langhorne J. Plasmodium chabaudi chabaudi: differential susceptibility of gene-targeted mice deficient in IL-10 to an erythrocytic-stage infection. Exp Parasitol (1996) 84(2):253-63. doi: 10.1006/expr.1996.0111.
47. Langhorne J, Meding SJ, Eichmann K, and Gillard SS. The response of CD4+ T cells to Plasmodium chabaudi chabaudi. Immunol Rev (1989) 112:71-94.
48. von der Weid T, and Langhorne J. The roles of cytokines produced in the immune response to the erythrocytic stages of mouse malarias. Immunobiology (1993) 189(3-4):397-418.
49. + memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity (2013) 39(4):758-69. doi: 10.1016/j.immuni.2013.08.031.
50. Mewono L, Matondo Maya DW, Matsiegui P-B, Agnandji ST, Kendjo E, Barondi F, et al E. 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 (2008) 19(1):30-6. doi: 10.1684/ecn.2008.0114.
51. Mewono L, Agnandji ST, Matondo Maya DW, Mouima A-MN, Iroungou BA, Issifou S, et al. Malaria antigen-mediated enhancement of interleukin-21 responses of peripheral blood mononuclear cells in African adults. Exp Parasitol (2009) 122(1):37-40. doi: 10.1016/j.exppara.2009.01.007.
52. Roetynck S, Olotu A, Simam J, Marsh K, Stockinger B, Urban B, et al. Phenotypic and functional profiling of CD4 T cell compartment in distinct populations of healthy adults with different antigenic exposure. PloS One (2013) 8(1):e55195. doi: 10.1371/journal.pone.0055195.
53. Chen Z, Laurence A, and O'Shea JJ. Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation. Semin Immunol (2007) 19(6):400-8. doi: 10.1016/j.smim.2007.10.015.
54. Keswani T, and Bhattacharyya A. Differential role of T regulatory and Th17 in Swiss mice infected with Plasmodium berghei ANKA and Plasmodium yoelii. Exp Parasitol (2014) 141:82-92. doi: 10.1016/j.exppara.2014.03.003.
55. Ishida H, Matsuzaki-Moriya C, Imai T, Yanagisawa K, Nojima Y, Suzue K, et al. Development of experimental cerebral malaria is independent of IL-23 and IL-17. Biochem Biophys Res Commun (2010) 402(4):790-5. doi: 10.1016/j.bbrc.2010.10.114.
56. Mastelic B, do Rosario APF, Veldhoen M, Renauld JC, Jarra W, Sponaas AM, et al. IL-22 Protects Against Liver Pathology and Lethality of an Experimental Blood-Stage Malaria Infection. Front Immunol (2012) 3:85. doi: 10.3389/fimmu.2012.00085.
57. Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, and Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol (2009) 10(8):857-63. doi: 10.1038/ni.1767.
58. Trifari S, Kaplan CD, Tran EH, Crellin NK, and Spits H. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol (2009) 10(8):864-71. doi: 10.1038/ni.1770.
59. Sonnenberg GF, Fouser LA, and Artis D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol (2011) 12(5):383-90. doi: 10.1038/ni.2025.
60. Koch O, Rockett K, Jallow M, Pinder M, Sisay-Joof F, and Kwiatkowski D. Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region. Genes Immun (2005) 6(4):312-8. doi:10.1038/sj.gene.6364214.
61. Nakayamada S, Takahashi H, Kanno Y, and O'Shea JJ. Helper T cell diversity and plasticity. Curr Opin Immunol (2012) 24(3):297-302. doi: 10.1016/j.coi.2012.01.014.
62. Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood (2006) 107(12):4781-9. doi: 10.1182/blood-2005-12-4818.
63. Darrah PA, Patel DT, De Luca PM, Lindsay RWB, Davey DF, Flynn BJ, et al. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med (2007) 13(7):843-50. doi:10.1038/nm1592.
64. Seder RA, Darrah PA, and Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol (2008) 8(4):247-58 doi: 10.1038/nri2274.
65. Huaman MC, Mullen GED, Long CA, and Mahanty S. Plasmodium falciparum apical membrane antigen 1 vaccine elicits multifunctional CD4 cytokine-producing and memory T cells. Vaccine (2009) 27(38):5239-46. doi: 10.1016/j.vaccine.2009.06.066.
66. Kastenmuller K, Espinosa DA, Trager L, Stoyanov C, Salazar AM, Pokalwar S, et al. Full-Length Plasmodium falciparum Circumsporozoite Protein Administered with Long-Chain Poly(I.C) or the Toll-Like Receptor 4 Agonist Glucopyranosyl Lipid Adjuvant-Stable Emulsion Elicits Potent Antibody and CD4+ T Cell Immunity and Protection in Mice. Infect Immun (2013) 81(3):789-800. doi: 10.1128/IAI.01108-12.
67. Metenou S, Dembele B, Konate S, Dolo H, Coulibaly YI, Diallo AA, et al. Filarial Infection Suppresses Malaria-Specific Multifunctional Th1 and Th17 Responses in Malaria and Filarial Coinfections. J Immunol (2011) 186(8):4725-33. doi: 10.4049/jimmunol.1003778.
68. Murphy KM, and Stockinger B. Effector T cell plasticity: flexibility in the face of changing circumstances. Nat Immunol (2010) 11(8):674-80. doi: 10.1038/ni.1899.
69. Lu KT, Kanno Y, Cannons JL, Handon R, Bible P, Elkahloun AG, et al. Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells. Immunity (2011) 35(4):622-32. doi: 10.1016/j.immuni.2011.07.015.
70. Freitas do Rosário AP, Lamb T, Spence P, Stephens R, Lang A, Roers A, et al. IL-27 promotes IL-10 production by effector Th1 CD4+ T cells: a critical mechanism for protection from severe immunopathology during malaria infection. J Immunol (2012) 188(3):1178-90. doi: 10.4049/jimmunol.1102755.
71. Couper KN, Blount DG, Wilson MS, Hafalla JC, Belkaid Y, Kamanaka M, et al. IL-10 from CD4+CD25-Foxp3-CD127-Adaptive Regulatory T Cells Modulates Parasite Clearance and Pathology during Malaria Infection. PLoS Pathog (2008) 4(2):e1000004. doi: 10.1371/journal.ppat.1000004.
72. Walther M, Jeffries D, Finney OC, Njie M, Ebonyi A, Deininger S, et al. Distinct Roles for FOXP3+ and FOXP3-CD4+ T Cells in Regulating Cellular Immunity to Uncomplicated and Severe Plasmodium falciparum Malaria. PLoS Pathog (2009) 5(4):e1000364. doi: 10.1371/journal.ppat.1000364.
73. Jagannathan P, Eccles-James I, Bowen K, Nankya F, Auma A, Wamala S, et al. IFNγ/IL-10 Co-producing Cells Dominate the CD4 Response to Malaria in Highly Exposed Children. PLoS Pathog (2014) 10(1):e1003864. doi: 10.1371/journal.ppat.1003864.
74. Portugal S, Moebius J, Skinner J, Doumbo S, Doumtabe D, Kone Y, et al. Exposure-Dependent Control of Malaria-Induced Inflammation in Children. PLoS Pathog (2014) 10(4):e1004079. doi: 10.1371/journal.ppat.1004079.
75. McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol (2007) 8(12):1390-7. doi: 10.1038/ni1539.
76. O'Garra A, Vieira P. T(H)1 cells control themselves by producing interleukin-10. Nat Rev Immunol (2007) 7(6):425-8. doi: 10.1038/nri2097.
77. Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M, et al. Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-β. Nature (2013) 484(7395):514-8. doi: 10.1038/nature10957.
78. Levings MK, Sangregorio R, Galbiati F, Squadrone S, de Waal Malefyt R, Roncarolo MG. IFN-a and IL-10 Induce the Differentiation of Human Type 1 T Regulatory Cells. J Immunol (2001) 166(9):5530-9. doi: 10.4049/jimmunol.166.9.5530.
79. Dikopoulos N, Bertoletti A, Kroger A, Hauser H, Schirmbeck R, Reimann J. Type I IFN Negatively Regulates CD8+ T Cell Responses through IL-10-Producing CD4+ T Regulatory 1 Cells. J Immunol (2004) 174(1):99-109. doi: 10.4049/jimmunol.174.1.99.
80. Zhang L, Yuan S, Cheng G, Guo B. Type I IFN Promotes IL-10 Production from T Cells to Suppress Th17 Cells and Th17-Associated Autoimmune Inflammation. PLoS One (2011) 6(12):e28432. doi: 10.1371/journal.pone.0028432.g008.
81. Corre B, Perrier J, El Khouri M, Cerboni S, Pellegrini S, Michel F. Type I interferon potentiates T-cell receptor mediated induction of IL-10-producing CD4+ T cells. Eur J Immunol (2013) 43(10):2730-40. doi: 10.1002/eji.201242977.
82. Illingworth J, Butler NS, Roetynck S, Mwacharo J, Pierce SK, Bejon P, et al. Chronic Exposure to Plasmodium falciparum Is Associated with Phenotypic Evidence of B and T Cell Exhaustion. J Immunol (2013) 190(3):1038-47. doi: 10.4049/jimmunol.1202438.
83. Butler NS, Moebius J, Pewe LL, Traore B, Doumbo OK, Tygrett LT, et al. Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood stage Plasmodium infection. Nat Immunol (2012) 13(2):188-95. doi: 10.1038/ni.2180.
84. Horne-Debets JM, Faleiro R, Karunarathne DS, Liu XQ, Lineburg KE, Poh CM, et al. PD-1 Dependent Exhaustion of CD8+ T Cells Drives Chronic Malaria. Cell Rep (2013) 5(5):1204-13. doi: 10.1016/j.celrep.2013.11.002.
85. Cubas RA, Mudd JC, Savoye A-L, Perreau M, van Grevenynghe J, Metcalf T, et al. Inadequate T follicular cell help impairs B cell immunity during HIV infection. Nat Med (2013) 19(4):494-9. doi: 10.1038/nm.3109.
86. Kimura A, and Kishimoto T. IL-6: Regulator of Treg/Th17 balance. Eur J Immunol (2010) 40(7):1830-5. doi: 10.1002/eji.201040391.
87. Barbi J, Pardoll D, and Pan F. Metabolic control of the Treg/Th17 axis. Immunol Rev (2013) 252(1):52-77. doi: 10.1111/imr.12029.
88. Stephens R, Albano FR, Quin S, Pascal BJ, Harrison V, Stockinger B, et al. 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 (2005) 106(5):1676-84. doi: http://dx.doi.org/10.1182/blood-2004-10-4047
89. Olszewski KL, Morrisey JM, Wilinski D, Burns JM, Vaidya AB, Rabinowitz JD, et al. Host-Parasite Interactions Revealed by Plasmodium falciparum Metabolomics. Cell Host Microbe (2009) 5(2):191-9. doi: 10.1016/j.chom.2009.01.004.
90. Kafsack BFC, and Llinás M. Eating at the Table of Another: Metabolomics of Host-Parasite Interactions. Cell Host Microbe (2010) 7(2):90-9. doi: 10.1016/j.chom.2010.01.008.
91. Nepom GT. MHC Class II Tetramers. J Immunol (2012) 188(6):2477-82. doi: 10.4049/jimmunol.1102398.
92. Cockburn IA, Amino R, Kelemen RK, Kuo SC, Tse S-W, Radtke A, et al. In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages. Proc Natl Acad Sci USA (2013) 110(22):9090-5. doi: 10.1073/pnas.1303858110.
93. Painter HJ, Altenhofen LM, Kafsack BFC, and Llinás M. Whole-genome analysis of Plasmodium spp. Utilizing a new agilent technologies DNA microarray platform. Methods Mol Biol (2013) 923:213-9. doi: 10.1007/978-1-62703-026-7_14.
94. Tse S-W, Cockburn IA, Zhang H, Scott AL, and Zavala F. Unique transcriptional profile of liver-resident memory CD8+ T cells induced by immunization with malaria sporozoites. Genes Immun (2013) 14(5):302-9. doi: 10.1038/gene.2013.20.
95. Salinas JL, Kissinger JC, Jones DP, and Galinski MR. Metabolomics in the fight against malaria. Mem Inst Oswaldo Cruz (2014) 109(5):589-97.
96. Franke-Fayard B, Waters AP, and Janse CJ. Real- time in vivo imaging of transgenic bioluminescent blood stages of rodent malaria parasites in mice. Nat Protoc (2006) 1(1):476-85. doi:10.1038/nprot.2006.69.
97. Tran TM, Samal B, Kirkness E, and Crompton PD. Systems immunology of human malaria. Trends Parasitol (2012) 28(6):248-57. doi: 10.1016/j.pt.2012.03.006.
98. Menard R, Tavares J, Cockburn I, Markus M, Zavala F, et al. Looking under the skin: the first steps in malarial infection and immunity. Nat Rev Microbiol (2013) 11(10):701-12. doi: 10.1038/nrmicro3111.