Skip to main content Accessibility help
×
Home

Immune activation and induction of memory: lessons learned from controlled human malaria infection with Plasmodium falciparum

  • ANJA SCHOLZEN (a1) and ROBERT W. SAUERWEIN (a1)

Summary

Controlled human malaria infections (CHMIs) are a powerful tool to assess the efficacy of drugs and/or vaccine candidates, but also to study anti-malarial immune responses at well-defined time points after infection. In this review, we discuss the insights that CHMI trials have provided into early immune activation and regulation during acute infection, and the capacity to induce and maintain immunological memory. Importantly, these studies show that a single infection is sufficient to induce long-lasting parasite-specific T- and B-cell memory responses, and suggest that blood-stage induced regulatory responses can limit inflammation both in ongoing and potentially future infections. As future perspective of investigation in CHMIs, we discuss the role of innate cell subsets, the interplay between innate and adaptive immune activation and the potential modulation of these responses after natural pre-exposure.

Copyright

Corresponding author

*Corresponding authors. Department of Medical Microbiology, Radboud university medical center, Route 268, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: +31 24 3614306. Fax: +31 24 3614666. E-mail: anja.scholzen@radboudumc.nl; robert.sauerwein@radboudumc.nl

References

Hide All
Arevalo-Herrera, M., Forero-Pena, D. A., Rubiano, K., Gomez-Hincapie, J., Martinez, N. L., Lopez-Perez, M., Castellanos, A., Cespedes, N., Palacios, R., Onate, J. M. and Herrera, S. (2014). Plasmodium vivax sporozoite challenge in malaria-naive and semi-immune Colombian volunteers. PLoS ONE 9, e99754.
Artavanis-Tsakonas, K., Eleme, K., McQueen, K. L., Cheng, N. W., Parham, P., Davis, D. M. and Riley, E. M. (2003). Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes. Journal of Immunology 171, 53965405.
Artis, D. and Spits, H. (2015). The biology of innate lymphoid cells. Nature 517, 293301.
Badr, G., Borhis, G., Lefevre, E. A., Chaoul, N., Deshayes, F., Dessirier, V., Lapree, G., Tsapis, A. and Richard, Y. (2008). BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells. Blood 111, 27442754.
Belderok, S. M., van den Hoek, A., Roeffen, W., Sauerwein, R. and Sonder, G. J. (2013). Adherence to chemoprophylaxis and Plasmodium falciparum anti-circumsporozoite seroconversion in a prospective cohort study of Dutch short-term travelers. PLoS ONE 8, e56863.
Bertho, N., Blancheteau, V. M., Setterblad, N., Laupeze, B., Lord, J. M., Drenou, B., Amiot, L., Charron, D. J., Fauchet, R. and Mooney, N. (2002). MHC class II-mediated apoptosis of mature dendritic cells proceeds by activation of the protein kinase C-delta isoenzyme. International Immunology 14, 935942.
Bijker, E. M., Bastiaens, G. J., Teirlinck, A. C., van Gemert, G. J., Graumans, W., van de Vegte-Bolmer, M., Siebelink-Stoter, R., Arens, T., Teelen, K., Nahrendorf, W., Remarque, E. J., Roeffen, W., Jansens, A., Zimmerman, D., Vos, M., van Schaijk, B. C., Wiersma, J., van der Ven, A. J., de Mast, Q., van Lieshout, L., Verweij, J. J., Hermsen, C. C., Scholzen, A. and Sauerwein, R. W. (2013). Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity. Proceedings of the National Academy of Sciences of the United States of America 110, 78627867.
Biswas, S., Choudhary, P., Elias, S. C., Miura, K., Milne, K. H., de Cassan, S. C., Collins, K. A., Halstead, F. D., Bliss, C. M., Ewer, K. J., Osier, F. H., Hodgson, S. H., Duncan, C. J., O'Hara, G. A., Long, C. A., Hill, A. V. and Draper, S. J. (2014). Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure. PLoS ONE 9, e107903.
Boswell, K. L., Paris, R., Boritz, E., Ambrozak, D., Yamamoto, T., Darko, S., Wloka, K., Wheatley, A., Narpala, S., McDermott, A., Roederer, M., Haubrich, R., Connors, M., Ake, J., Douek, D. C., Kim, J., Petrovas, C. and Koup, R. A. (2014). Loss of circulating CD4 T cells with B cell helper function during chronic HIV infection. PLoS Pathogens 10, e1003853.
Brinkman, C. C., Peske, J. D. and Engelhard, V. H. (2013). Peripheral tissue homing receptor control of naive, effector, and memory CD8 T cell localization in lymphoid and non-lymphoid tissues. Frontiers in Immunology 4, 241.
Chulay, J. D., Schneider, I., Cosgriff, T. M., Hoffman, S. L., Ballou, W. R., Quakyi, I. A., Carter, R., Trosper, J. H. and Hockmeyer, W. T. (1986). Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum. American Journal of Tropical Medicine and Hygiene 35, 6668.
Church, L. W., Le, T. P., Bryan, J. P., Gordon, D. M., Edelman, R., Fries, L., Davis, J. R., Herrington, D. A., Clyde, D. F., Shmuklarsky, M. J., Schneider, I., McGovern, T. W., Chulay, J. D., Ballou, W. R. and Hoffman, S. L. (1997). Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge. Journal of Infectious Diseases 175, 915920.
Cobelens, F. G., Verhave, J. P., Leentvaar-Kuijpers, A. and Kager, P. A. (1998). Testing for anti-circumsporozoite and anti-blood-stage antibodies for epidemiologic assessment of Plasmodium falciparum infection in travelers. American Journal of Tropical Medicine and Hygiene 58, 7580.
Collins, W. E. and Jeffery, G. M. (1999 a). A retrospective examination of secondary sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity following secondary infection. American Journal of Tropical Medicine and Hygiene 61, 2035.
Collins, W. E. and Jeffery, G. M. (1999 b). A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum in patients previously infected with heterologous species of Plasmodium: effect on development of parasitologic and clinical immunity. American Journal of Tropical Medicine and Hygiene 61, 3643.
Collins, W. E. and Jeffery, G. M. (1999 c). A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity during primary infection. American Journal of Tropical Medicine and Hygiene 61, 419.
Collins, W. E., Jeffery, G. M. and Roberts, J. M. (2004). A retrospective examination of reinfection of humans with Plasmodium vivax. American Journal of Tropical Medicine and Hygiene 70, 642644.
Conroy, A., Serghides, L., Finney, C., Owino, S. O., Kumar, S., Gowda, D. C., Liles, W. C., Moore, J. M. and Kain, K. C. (2009). C5a enhances dysregulated inflammatory and angiogenic responses to malaria in vitro: potential implications for placental malaria. PLoS ONE 4, e4953.
de Mast, Q., Groot, E., Lenting, P. J., de Groot, P. G., McCall, M., Sauerwein, R. W., Fijnheer, R. and van der Ven, A. (2007). Thrombocytopenia and release of activated von Willebrand factor during early Plasmodium falciparum malaria. Journal of Infectious Diseases 196, 622628.
De Mast, Q., Sweep, F. C., McCall, M., Geurts-Moespot, A., Hermsen, C., Calandra, T., Netea, M. G., Sauerwein, R. W. and van der Ven, A. J. (2008). A decrease of plasma macrophage migration inhibitory factor concentration is associated with lower numbers of circulating lymphocytes in experimental Plasmodium falciparum malaria. Parasite Immunology 30, 133138.
de Mast, Q., Nadjm, B., Reyburn, H., Kemna, E. H., Amos, B., Laarakkers, C. M., Silalye, S., Verhoef, H., Sauerwein, R. W., Swinkels, D. W. and van der Ven, A. J. (2009 a). Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection. Journal of Infectious Diseases 199, 253262.
de Mast, Q., van Dongen-Lases, E. C., Swinkels, D. W., Nieman, A. E., Roestenberg, M., Druilhe, P., Arens, T. A., Luty, A. J., Hermsen, C. C., Sauerwein, R. W. and van der Ven, A. J. (2009 b). Mild increases in serum hepcidin and interleukin-6 concentrations impair iron incorporation in haemoglobin during an experimental human malaria infection. British Journal of Haematology 145, 657664.
Dobel, T., Kunze, A., Babatz, J., Trankner, K., Ludwig, A., Schmitz, M., Enk, A. and Schakel, K. (2013). FcgammaRIII (CD16) equips immature 6-sulfo LacNAc-expressing dendritic cells (slanDCs) with a unique capacity to handle IgG-complexed antigens. Blood 121, 36093618.
D'Ombrain, M. C., Hansen, D. S., Simpson, K. M. and Schofield, L. (2007). gammadelta-T cells expressing NK receptors predominate over NK cells and conventional T cells in the innate IFN-gamma response to Plasmodium falciparum malaria. European Journal of Immunology 37, 18641873.
Donati, D., Zhang, L. P., Chene, A., Chen, Q., Flick, K., Nystrom, M., Wahlgren, M. and Bejarano, M. T. (2004). Identification of a polyclonal B-cell activator in Plasmodium falciparum. Infection and Immunity 72, 54125418.
Druilhe, P., Hagan, P. and Rook, G. A. (2002). The importance of models of infection in the study of disease resistance. Trends in Microbiology 10, S38S46.
Duncan, C. J. and Draper, S. J. (2012). Controlled human blood stage malaria infection: current status and potential applications. American Journal of Tropical Medicine and Hygiene 86, 561565.
Elias, S. C., Collins, K. A., Halstead, F. D., Choudhary, P., Bliss, C. M., Ewer, K. J., Sheehy, S. H., Duncan, C. J., Biswas, S., Hill, A. V. and Draper, S. J. (2013). Assessment of immune interference, antagonism, and diversion following human immunization with biallelic blood-stage malaria viral-vectored vaccines and controlled malaria infection. Journal of Immunology 190, 11351147.
Elias, S. C., Choudhary, P., de Cassan, S. C., Biswas, S., Collins, K. A., Halstead, F. D., Bliss, C. M., Ewer, K. J., Hodgson, S. H., Duncan, C. J., Hill, A. V. and Draper, S. J. (2014). Analysis of human B-cell responses following ChAd63-MVA MSP1 and AMA1 immunization and controlled malaria infection. Immunology 141, 628644.
Elliott, S. R., Payne, P. D., Duffy, M. F., Byrne, T. J., Tham, W. H., Rogerson, S. J., Brown, G. V. and Eisen, D. P. (2007). Antibody recognition of heterologous variant surface antigens after a single Plasmodium falciparum infection in previously naive adults. American Journal of Tropical Medicine and Hygiene 76, 860864.
Engwerda, C. R., Minigo, G., Amante, F. H. and McCarthy, J. S. (2012). Experimentally induced blood stage malaria infection as a tool for clinical research. Trends in Parasitology 28, 515521.
Epstein, J. E., Rao, S., Williams, F., Freilich, D., Luke, T., Sedegah, M., de la Vega, P., Sacci, J., Richie, T. L. and Hoffman, S. L. (2007). Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update. Journal of Infectious Diseases 196, 145154.
Erdman, L. K., Finney, C. A., Liles, W. C. and Kain, K. C. (2008). Inflammatory pathways in malaria infection: TLRs share the stage with other components of innate immunity. Molecular and Biochemical Parasitology 162, 105111.
Feachem, R. G., Phillips, A. A., Hwang, J., Cotter, C., Wielgosz, B., Greenwood, B. M., Sabot, O., Rodriguez, M. H., Abeyasinghe, R. R., Ghebreyesus, T. A. and Snow, R. W. (2010). Shrinking the malaria map: progress and prospects. Lancet 376, 15661578.
Frevert, U., Nacer, A., Cabrera, M., Movila, A. and Leberl, M. (2014). Imaging Plasmodium immunobiology in the liver, brain, and lung. Parasitology International 63, 171186.
Fuertes Marraco, S. A., Scott, C. L., Bouillet, P., Ives, A., Masina, S., Vremec, D., Jansen, E. S., O'Reilly, L. A., Schneider, P., Fasel, N., Shortman, K., Strasser, A. and Acha-Orbea, H. (2011). Type I interferon drives dendritic cell apoptosis via multiple BH3-only proteins following activation by PolyIC in vivo. PLoS ONE 6, e20189.
Gun, S. Y., Claser, C., Tan, K. S. and Renia, L. (2014). Interferons and interferon regulatory factors in malaria. Mediators of Inflammation 2014, 243713.
Harpaz, R., Edelman, R., Wasserman, S. S., Levine, M. M., Davis, J. R. and Sztein, M. B. (1992). Serum cytokine profiles in experimental human malaria. Relationship to protection and disease course after challenge. Journal of Clinical Investigation 90, 515523.
Hermsen, C. C., Konijnenberg, Y., Mulder, L., Loe, C., van Deuren, M., van der Meer, J. W., van Mierlo, G. J., Eling, W. M., Hack, C. E. and Sauerwein, R. W. (2003). Circulating concentrations of soluble granzyme A and B increase during natural and experimental Plasmodium falciparum infections. Clinical and Experimental Immunology 132, 467472.
Herrera, S., Fernandez, O., Manzano, M. R., Murrain, B., Vergara, J., Blanco, P., Palacios, R., Velez, J. D., Epstein, J. E., Chen-Mok, M., Reed, Z. H. and Arevalo-Herrera, M. (2009). Successful sporozoite challenge model in human volunteers with Plasmodium vivax strain derived from human donors. American Journal of Tropical Medicine and Hygiene 81, 740746.
Herrera, S., Solarte, Y., Jordan-Villegas, A., Echavarria, J. F., Rocha, L., Palacios, R., Ramirez, O., Velez, J. D., Epstein, J. E., Richie, T. L. and Arevalo-Herrera, M. (2011). Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers. American Journal of Tropical Medicine and Hygiene 84, 411.
Herrington, D. A., Clyde, D. F., Murphy, J. R., Baqar, S., Levine, M. M., do Rosario, V. and Hollingdale, M. R. (1988). A model for Plasmodium falciparum sporozoite challenge and very early therapy of parasitaemia for efficacy studies of sporozoite vaccines. Tropical and Geographical Medicine 40, 124127.
Hofer, T., Krichevsky, O. and Altan-Bonnet, G. (2012). Competition for IL-2 between regulatory and effector T cells to chisel immune responses. Frontiers in Immunology 3, 268.
Horowitz, A., Newman, K. C., Evans, J. H., Korbel, D. S., Davis, D. M. and Riley, E. M. (2010). Cross-talk between T cells and NK cells generates rapid effector responses to Plasmodium falciparum-infected erythrocytes. Journal of Immunology 184, 60436052.
Jelinek, T., Nothdurft, H. D. and Loscher, T. (1995). Evaluation of circumsporozoite antibody testing as a sero-epidemiological tool for the detection of Plasmodium falciparum infection in non-immune travelers. Tropical Medicine and Parasitology 46, 154157.
Jelinek, T., Bluml, A., Loscher, T. and Nothdurft, H. D. (1998). Assessing the incidence of infection with Plasmodium falciparum among international travelers. American Journal of Tropical Medicine and Hygiene 59, 3537.
Knappik, M., Peyerl-Hoffmann, G. and Jelinek, T. (2002). Plasmodium falciparum: use of a NANP19 antibody-test for the detection of infection in non-immune travellers. Tropical Medicine and International Health 7, 652656.
Korbel, D. S., Newman, K. C., Almeida, C. R., Davis, D. M. and Riley, E. M. (2005). Heterogeneous human NK cell responses to Plasmodium falciparum-infected erythrocytes. Journal of Immunology 175, 74667473.
Kumsiri, R., Potup, P., Chotivanich, K., Petmitr, S., Kalambaheti, T. and Maneerat, Y. (2010). Blood stage Plasmodium falciparum antigens induce T cell independent immunoglobulin production via B cell activation factor of the TNF family (BAFF) pathway. Acta Tropica 116, 217226.
Kushwah, R. and Hu, J. (2010). Dendritic cell apoptosis: regulation of tolerance versus immunity. Journal of Immunology 185, 795802.
Langhorne, J., Ndungu, F. M., Sponaas, A. M. and Marsh, K. (2008). Immunity to malaria: more questions than answers. Nature Immunology 9, 725732.
Lavstsen, T., Magistrado, P., Hermsen, C. C., Salanti, A., Jensen, A. T., Sauerwein, R., Hviid, L., Theander, T. G. and Staalsoe, T. (2005). Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans. Malaria Journal 4, 21.
Liehl, P., Zuzarte-Luis, V., Chan, J., Zillinger, T., Baptista, F., Carapau, D., Konert, M., Hanson, K. K., Carret, C., Lassnig, C., Muller, M., Kalinke, U., Saeed, M., Chora, A. F., Golenbock, D. T., Strobl, B., Prudencio, M., Coelho, L. P., Kappe, S. H., Superti-Furga, G., Pichlmair, A., Vigario, A. M., Rice, C. M., Fitzgerald, K. A., Barchet, W. and Mota, M. M. (2014). Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection. Nature Medicine 20, 4753.
Liu, Z. and Roche, P. A. (2015). Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells. Frontiers in Physiology 6, 1.
Locci, M., Havenar-Daughton, C., Landais, E., Wu, J., Kroenke, M. A., Arlehamn, C. L., Su, L. F., Cubas, R., Davis, M. M., Sette, A., Haddad, E. K., International AIDS Vaccine Initiative Protocol C Principal Investigators, Poignard, P. and Crotty, S. (2013). Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and correlate with broadly neutralizing HIV antibody responses. Immunity 39, 758769.
Lovegrove, F. E., Pena-Castillo, L., Mohammad, N., Liles, W. C., Hughes, T. R. and Kain, K. C. (2006). Simultaneous host and parasite expression profiling identifies tissue-specific transcriptional programs associated with susceptibility or resistance to experimental cerebral malaria. BMC Genomics 7, 295.
Martini, F., Paglia, M. G., Montesano, C., Enders, P. J., Gentile, M., Pauza, C. D., Gioia, C., Colizzi, V., Narciso, P., Pucillo, L. P. and Poccia, F. (2003). V gamma 9 V delta 2T-cell anergy and complementarity-determining region 3-specific depletion during paroxysm of nonendemic malaria infection. Infection and Immunity 71, 29452949.
McCall, M. B., Netea, M. G., Hermsen, C. C., Jansen, T., Jacobs, L., Golenbock, D., van der Ven, A. J. and Sauerwein, R. W. (2007). Plasmodium falciparum infection causes proinflammatory priming of human TLR responses. Journal of Immunology 179, 162171.
McCall, M. B., Roestenberg, M., Ploemen, I., Teirlinck, A., Hopman, J., de Mast, Q., Dolo, A., Doumbo, O. K., Luty, A., van der Ven, A. J., Hermsen, C. C. and Sauerwein, R. W. (2010). Memory-like IFN-gamma response by NK cells following malaria infection reveals the crucial role of T cells in NK cell activation by P. falciparum. European Journal of Immunology 40, 34723477.
McCarthy, J. S., Sekuloski, S., Griffin, P. M., Elliott, S., Douglas, N., Peatey, C., Rockett, R., O'Rourke, P., Marquart, L., Hermsen, C., Duparc, S., Mohrle, J., Trenholme, K. R. and Humberstone, A. J. (2011). A pilot randomised trial of induced blood-stage Plasmodium falciparum infections in healthy volunteers for testing efficacy of new antimalarial drugs. PLoS ONE 6, e21914.
McHeyzer-Williams, M., Okitsu, S., Wang, N. and McHeyzer-Williams, L. (2012). Molecular programming of B cell memory. Nature Reviews Immunology 12, 2434.
Mestas, J. and Hughes, C. C. (2004). Of mice and not men: differences between mouse and human immunology. Journal of Immunology 172, 27312738.
Miller, J. L., Sack, B. K., Baldwin, M., Vaughan, A. M. and Kappe, S. H. (2014). Interferon-mediated innate immune responses against malaria parasite liver stages. Cell Reports 7, 436447.
Mitchell, A. J., Roediger, B. and Weninger, W. (2014). Monocyte homeostasis and the plasticity of inflammatory monocytes. Cellular Immunology 291, 2231.
Molineaux, L., Trauble, M., Collins, W. E., Jeffery, G. M. and Dietz, K. (2002). Malaria therapy reinoculation data suggest individual variation of an innate immune response and independent acquisition of antiparasitic and antitoxic immunities. Transactions of the Royal Society of Tropical Medicine and Hygiene 96, 205209.
Molle, I., Petersen, E. and Buhl, M. R. (1999). Retrospective evaluation of exposure to P. falciparum using antibodies to circumsporozoite protein and to cultured P. falciparum antigens. Scandinavian Journal of Infectious Diseases 31, 6971.
Nahrendorf, W., Scholzen, A., Bijker, E. M., Teirlinck, A. C., Bastiaens, G. J., Schats, R., Hermsen, C. C., Visser, L. G., Langhorne, J. and Sauerwein, R. W. (2014). Memory B-cell and antibody responses induced by Plasmodium falciparum sporozoite immunization. Journal of Infectious Diseases 210, 19811990.
Nduati, E. W., Ng, D. H., Ndungu, F. M., Gardner, P., Urban, B. C. and Langhorne, J. (2010). Distinct kinetics of memory B-cell and plasma-cell responses in peripheral blood following a blood-stage Plasmodium chabaudi infection in mice. PLoS ONE 5, e15007.
Nganou-Makamdop, K., van Gemert, G. J., Arens, T., Hermsen, C. C. and Sauerwein, R. W. (2012). Long term protection after immunization with P. berghei sporozoites correlates with sustained IFNgamma responses of hepatic CD8+ memory T cells. PLoS ONE 7, e36508.
Nothdurft, H. D., Jelinek, T., Bluml, A., von Sonnenburg, F. and Loscher, T. (1999). Seroconversion to circumsporozoite antigen of Plasmodium falciparum demonstrates a high risk of malaria transmission in travelers to East Africa. Clinical Infectious Diseases 28, 641642.
Obiero, J. M., Shekalaghe, S., Hermsen, C. C., Mpina, M., Bijker, E. M., Roestenberg, M., Teelen, K., Billingsley, P. F., Sim, B. K., James, E. R., Daubenberger, C. A., Hoffman, S. L., Abdulla, S., Sauerwein, R. W. and Scholzen, A. (2015). Impact of malaria pre-exposure on anti-parasite cellular and humoral immune responses after controlled human malaria infection. Infection and Immunity 83, 21852196.
Ockenhouse, C. F., Hu, W. C., Kester, K. E., Cummings, J. F., Stewart, A., Heppner, D. G., Jedlicka, A. E., Scott, A. L., Wolfe, N. D., Vahey, M. and Burke, D. S. (2006). Common and divergent immune response signaling pathways discovered in peripheral blood mononuclear cell gene expression patterns in presymptomatic and clinically apparent malaria. Infection and Immunity 74, 55615573.
Orlov, M., Vaida, F., Finney, O. C., Smith, D. M., Talley, A. K., Wang, R., Kappe, S. H., Deng, Q., Schooley, R. T. and Duffy, P. E. (2012). P. falciparum enhances HIV replication in an experimental malaria challenge system. PLoS ONE 7, e39000.
Peters, J., Fowler, E., Gatton, M., Chen, N., Saul, A. and Cheng, Q. (2002). High diversity and rapid changeover of expressed var genes during the acute phase of Plasmodium falciparum infections in human volunteers. Proceedings of the National Academy of Sciences of the United States of America 99, 1068910694.
Pichyangkul, S., Yongvanitchit, K., Kum-arb, U., Hemmi, H., Akira, S., Krieg, A. M., Heppner, D. G., Stewart, V. A., Hasegawa, H., Looareesuwan, S., Shanks, G. D. and Miller, R. S. (2004). Malaria blood stage parasites activate human plasmacytoid dendritic cells and murine dendritic cells through a Toll-like receptor 9-dependent pathway. Journal of Immunology 172, 49264933.
Portugal, S., Pierce, S. K. and Crompton, P. D. (2013). Young lives lost as B cells falter: what we are learning about antibody responses in malaria. Journal of Immunology 190, 30393046.
Riley, E. M. and Stewart, V. A. (2013). Immune mechanisms in malaria: new insights in vaccine development. Nature Medicine 19, 168178.
Roestenberg, M., McCall, M., Mollnes, T. E., van Deuren, M., Sprong, T., Klasen, I., Hermsen, C. C., Sauerwein, R. W. and van der Ven, A. (2007). Complement activation in experimental human malaria infection. Transactions of the Royal Society of Tropical Medicine and Hygiene 101, 643649.
Roestenberg, M., O'Hara, G. A., Duncan, C. J., Epstein, J. E., Edwards, N. J., Scholzen, A., van der Ven, A. J., Hermsen, C. C., Hill, A. V. and Sauerwein, R. W. (2012). Comparison of clinical and parasitological data from controlled human malaria infection trials. PLoS ONE 7, e38434.
Roestenberg, M., Bijker, E. M., Sim, B. K., Billingsley, P. F., James, E. R., Bastiaens, G. J., Teirlinck, A. C., Scholzen, A., Teelen, K., Arens, T., van der Ven, A. J., Gunasekera, A., Chakravarty, S., Velmurugan, S., Hermsen, C. C., Sauerwein, R. W. and Hoffman, S. L. (2013). Controlled human malaria infections by intradermal injection of cryopreserved Plasmodium falciparum sporozoites. American Journal of Tropical Medicine and Hygiene 88, 513.
Rzepczyk, C. M., Stamatiou, S., Anderson, K., Stowers, A., Cheng, Q., Saul, A., Allworth, A., McCormack, J., Whitby, M., Olive, C. and Lawrence, G. (1996). Experimental human Plasmodium falciparum infections: longitudinal analysis of lymphocyte responses with particular reference to gamma delta T cells. Scandinavian Journal of Immunology 43, 219227.
Sallusto, F., Geginat, J. and Lanzavecchia, A. (2004). Central memory and effector memory T cell subsets: function, generation, and maintenance. Annual Review of Immunology 22, 745763.
Sauerwein, R. W., Roestenberg, M. and Moorthy, V. S. (2011). Experimental human challenge infections can accelerate clinical malaria vaccine development. Nature Reviews Immunology 11, 5764.
Schenkel, J. M. and Masopust, D. (2014). Tissue-resident memory T cells. Immunity 41, 886897.
Scholzen, A. and Sauerwein, R. W. (2013). How malaria modulates memory: activation and dysregulation of B cells in Plasmodium infection. Trends in Parasitology 29, 252262.
Scholzen, A., Mittag, D., Rogerson, S. J., Cooke, B. M. and Plebanski, M. (2009). Plasmodium falciparum-mediated induction of human CD25Foxp3 CD4T cells is independent of direct TCR stimulation and requires IL-2, IL-10 and TGFbeta. PLoS Pathogens 5, e1000543.
Scholzen, A., Minigo, G. and Plebanski, M. (2010). Heroes or villains? T regulatory cells in malaria infection. Trends in Parasitology 26, 1625.
Scholzen, A., Teirlinck, A. C., Bijker, E. M., Roestenberg, M., Hermsen, C. C., Hoffman, S. L. and Sauerwein, R. W. (2014). BAFF and BAFF receptor levels correlate with B cell subset activation and redistribution in controlled human malaria infection. Journal of Immunology 192, 37193729.
Seder, R. A., Chang, L. J., Enama, M. E., Zephir, K. L., Sarwar, U. N., Gordon, I. J., Holman, L. A., James, E. R., Billingsley, P. F., Gunasekera, A., Richman, A., Chakravarty, S., Manoj, A., Velmurugan, S., Li, M., Ruben, A. J., Li, T., Eappen, A. G., Stafford, R. E., Plummer, S. H., Hendel, C. S., Novik, L., Costner, P. J., Mendoza, F. H., Saunders, J. G., Nason, M. C., Richardson, J. H., Murphy, J., Davidson, S. A., Richie, T. L., et al. (2013). Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341, 13591365.
Seed, C. R., Hamzah, J. and Davis, T. M. (2006). Evidence for undetected malaria infection in non-immune Australian travellers not taking chemoprophylaxis. Acta Tropica 99, 6266.
Sheehy, S. H., Spencer, A. J., Douglas, A. D., Sim, B. K., Longley, R. J., Edwards, N. J., Poulton, I. D., Kimani, D., Williams, A. R., Anagnostou, N. A., Roberts, R., Kerridge, S., Voysey, M., James, E. R., Billingsley, P. F., Gunasekera, A., Lawrie, A. M., Hoffman, S. L. and Hill, A. V. (2013). Optimising controlled human malaria infection studies using cryopreserved parasites administered by needle and syringe. PLoS ONE 8, e65960.
Snounou, G. and Perignon, J. L. (2013). Malariotherapy – insanity at the service of malariology. Advances in Parasitology 81, 223255.
Stephens, R., Culleton, R. L. and Lamb, T. J. (2012). The contribution of Plasmodium chabaudi to our understanding of malaria. Trends in Parasitology 28, 7382.
Struik, S. S. and Riley, E. M. (2004). Does malaria suffer from lack of memory? Immunological Reviews 201, 268290.
Talley, A. K., Healy, S. A., Finney, O. C., Murphy, S. C., Kublin, J., Salas, C. J., Lundebjerg, S., Gilbert, P., Van Voorhis, W. C., Whisler, J., Wang, R., Ockenhouse, C. F., Heppner, D. G., Kappe, S. H. and Duffy, P. E. (2014). Safety and comparability of controlled human Plasmodium falciparum infection by mosquito bite in malaria-naive subjects at a new facility for sporozoite challenge. PLoS ONE 9, e109654.
Teirlinck, A. C., McCall, M. B., Roestenberg, M., Scholzen, A., Woestenenk, R., de Mast, Q., van der Ven, A. J., Hermsen, C. C., Luty, A. J. and Sauerwein, R. W. (2011). Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans. PLoS Pathogens 7, e1002389.
Teirlinck, A. C., Roestenberg, M., van de Vegte-Bolmer, M., Scholzen, A., Heinrichs, M. J., Siebelink-Stoter, R., Graumans, W., van Gemert, G. J., Teelen, K., Vos, M. W., Nganou-Makamdop, K., Borrmann, S., Rozier, Y. P., Erkens, M. A., Luty, A. J., Hermsen, C. C., Sim, B. K., van Lieshout, L., Hoffman, S. L., Visser, L. G. and Sauerwein, R. W. (2013). NF135.C10: a new Plasmodium falciparum clone for controlled human malaria infections. Journal of Infectious Diseases 207, 656660.
Todryk, S. M., Walther, M., Bejon, P., Hutchings, C., Thompson, F. M., Urban, B. C., Porter, D. W. and Hill, A. V. (2009). Multiple functions of human T cells generated by experimental malaria challenge. European Journal of Immunology 39, 30423051.
Turner, L., Wang, C. W., Lavstsen, T., Mwakalinga, S. B., Sauerwein, R. W., Hermsen, C. C. and Theander, T. G. (2011). Antibodies against PfEMP1, RIFIN, MSP3 and GLURP are acquired during controlled Plasmodium falciparum malaria infections in naive volunteers. PLoS ONE 6, e29025.
Verhage, D. F., Telgt, D. S., Bousema, J. T., Hermsen, C. C., van Gemert, G. J., van der Meer, J. W. and Sauerwein, R. W. (2005). Clinical outcome of experimental human malaria induced by Plasmodium falciparum-infected mosquitoes. Netherlands Journal of Medicine 63, 5258.
Walker, K. M., Okitsu, S., Porter, D. W., Duncan, C., Amacker, M., Pluschke, G., Cavanagh, D. R., Hill, A. V. and Todryk, S. M. (2014). Antibody and T cell responses associated with experimental human malaria infection or vaccination show limited relationships. Immunology 145, 7181.
Walther, M., Tongren, J. E., Andrews, L., Korbel, D., King, E., Fletcher, H., Andersen, R. F., Bejon, P., Thompson, F., Dunachie, S. J., Edele, F., de Souza, J. B., Sinden, R. E., Gilbert, S. C., Riley, E. M. and Hill, A. V. (2005). Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity 23, 287296.
Walther, M., Woodruff, J., Edele, F., Jeffries, D., Tongren, J. E., King, E., Andrews, L., Bejon, P., Gilbert, S. C., De Souza, J. B., Sinden, R., Hill, A. V. and Riley, E. M. (2006). Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes. Journal of Immunology 177, 57365745.
Wang, C. W., Hermsen, C. C., Sauerwein, R. W., Arnot, D. E., Theander, T. G. and Lavstsen, T. (2009). The Plasmodium falciparum var gene transcription strategy at the onset of blood stage infection in a human volunteer. Parasitology International 58, 478480.
WHO (2013). World Malaria Report 2013. World Health Organization, WHO Press.
Woodberry, T., Minigo, G., Piera, K. A., Amante, F. H., Pinzon-Charry, A., Good, M. F., Lopez, J. A., Engwerda, C. R., McCarthy, J. S. and Anstey, N. M. (2012). Low-level Plasmodium falciparum blood-stage infection causes dendritic cell apoptosis and dysfunction in healthy volunteers. Journal of Infectious Diseases 206, 333340.
Wykes, M. N. and Good, M. F. (2008). What really happens to dendritic cells during malaria? Nature Reviews Microbiology 6, 864870.
Yang, K. and Chi, H. (2012). mTOR and metabolic pathways in T cell quiescence and functional activation. Seminars in Immunology 24, 421428.

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed