Malaria infection gives rise to host response which is regulated by both the immune system as well as by the environmental factors. In this paper, we discuss the immune regulation of malaria blood stage infection in humans, focusing on Plasmodium falciparum, the most widely spread and dangerous of the human malaria parasites. We also propose some differential equations which describe the dynamics of the immune cells and their cytokines interacting against the blood stage malaria parasite. Then we study the stability of the system at the equilibrium point.

mathematical modelling, dynamics of immune cells, stability analysis.

Received: December 21, 2020; Revised: February 5, 2021; Accepted: February 10, 2021; Published: February 15, 2021

How to cite this article: Aminou M. Layaka, Bakari Abbo, Mahamat S. Daoussa Haggar and Youssouf Paré, Modelling and stability analysis of immune regulatory mechanisms during malaria blood stage infection, Advances in Differential Equations and Control Processes 24(1) (2021), 11-39. DOI: 10.17654/DE024010011

This Open Access Article is Licensed under Creative Commons Attribution 4.0 International License

References:

[1] A. K. Abbas, K. M. Murphy and A. Sher, Functional diversity of helper T lymphocytes, Nature 383 (1996), 787-793.
[2] N. Ahlborg, Immune response to repeat sequences of the Plasmodium falciparum malaria antigen Pf 332, Doctoral Thesis from the Department of Immunology, Stockholm Univ., 2005.
[3] A. I. Alayash, Oxygen therapeutics: can we tame haemoglobin? Nat. Rev. Drug Discov. 3 (2004), 152-159.
[4] A. C. Allison and E. Eugui, A radical interpretation of immunity to malarial parasites, Lancet 2 (1982), 1431-1433.
[5] R. M. Anderson, R. M. May and S. Gupta, Nonlinear phenomena in host parasite interactions, Parasitology 99 (1989).
[6] C. Aucan, Y. Traore, F. Tall, B. Nacro, T. Traore-Leroux, F. Fumoux and P. Rihet, High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria, Infect. Immun. 68 (2000), 1252-1258.
[7] C. Beauchemin, Modelling the immune system, Department of Physics, University of Alberta, 2002.
[8] S. Bereczky, S. M. Montgomery, M. Troye-Blomberg, I. Rooth, M. A. Shaw and A. Farnert, Elevated anti-malarial IgE in asymptomatic individuals is associated with reduced risk for subsequent clinical malaria, Int. J. Parasitol. 34 (2004), 935-942.
[9] J. D. Kurtis, D. E. Lanar, M. Opollo and P. E. Duffy, Interleukin-10 responses to liver stage antigen I predict human resistance to Plasmodium falciparum, Infect. Immun. 67 (1999), 3424-3429.
[10] C. Bogdan, Nitric oxide and the immune response, Nat. Immunol. 2 (2001), 907-916.
[11] C. Bogdan, Y. Vodovotz, J. Paik, Q. W. Xie and C. Nathan, Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages, J. Leukoc. Biol. 55 (1994), 227-233.
[12] A. K. Bolad, Antibody responses in Plasmodium falciparum malaria and their relation to protection against disease, Doctoral Thesis, Stockholm University, Sweden, 2004.
[13] H. Bouharoun-Tayoun, P. Attanath, A. Sabchareon, T. Chongsuphajaisiddhi and P. Druilhe, Antibodies that protect humans against Plasmodium falciparum blood stage do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes, J. Exp. Med. 172 (1990), 1633-1641.
[14] H. Bouharoun-Tayoun, C. Oeuvray, F. Lunel and P. Druilhe, Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages, J. Exp. Med. 182 (1995), 409-418.
[15] H. Bouharoun-Tayoun and P. Druilhe, Antibodies in Plasmodium falciparum malaria: what matters most, quantity or quality? Mem. Inst. Oswaldo Cruz 87(Suppl 3) (1992), 229-234.
[16] W. Bowers, A. Ghaffar and G. Mayer, Immunology, School of Medicine, Univ. of South Carolina, 2004.
[17] R. G. Brackett and R. L. Jacobs, Serum inhibition of merozoite dispersal from Plasmodium falciparum schizonts: indicator of immune status, Infect. Immun. 31 (1981), 1203-1208.
[18] L. R. Brunet, Nitric oxide in parasitic infections, Int. Immunopharmacol. 1 (2001), 1457-1467.
[19] C. Calissano, D. Modiano, B. S. Sirima, A. Konate, I. Sanou, A. Sawadogo, H. Perlmann et al., IgE antibodies to Plasmodium falciparum and severity of malaria in children of one ethnic group living in Burkina Faso, Am. J. Trop. Med. Hyg. 69(1) (2003), 31-35.
[20] J. Carlson, G. Holmquist, D. W. Taylor, P. Perlmann and M. Wahlgren, Antibodies to a histidine-rich protein (Pf HRP1) disrupt spontaneously formed Plasmodium falciparum erythrocytes rosettes, Proc. Natl. Acad. Sci. USA 87 (1990), 2511-2515.
[21] L. H. Carvalho, G. Sano, J. C. Hafalla, A. Morrot, M. A. Curotto de Lafaille and F. Zorata, IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T cells responses against malaria liver stages, Nat. Med. 8 (2002), 166-170.
[22] S. W. Chemsue, J. H. Ruth, K. Warmington, P. Lincoln and S. I. Kunkel, In vitro regulation of macrophage. IL-12 production during type 1 and type 2 cytokine-mediated granuloma formation, J. Immunol. 155 (1995).
[23] I. A. Clark and W. B. Cowden, The pathophysiology of falciparum malaria, Pharmacol. Ther. 99 (2003), 221-260.
[24] R. L. Coffman, B. K. Seymour, D. A. Lebman et al., The role of helper T cell products in mouse B cell differentiation and isotype regulation, Immunol. Rev. 102 (1988), 5-28.
[25] J. M. Crutcher, M. Stevenson, M. Sedegah and S. L. Hoffman, Interleukin12 and malaria, Res. Immunol. 146 (1995), 552-559.
[26] A. d’Andrea, M. Aste-Amezaga, N. M. Valianta, X. Ma, M. Kubin and G. Trinchieri, IL-10 inhibits human lymphocyte IFN- production by suppressing IL-12 synthesis in accessory cells, J. Exp. Med. 178 (1993), 1041-1048.
[27] R. de Waal Malefijt, R. J. Haanen, H. Spits, M. G. Roncarolo et al., IL-10 and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via down-regulation of class II major histocompatibility complex expression, J. Exp. Med. 174 (1991), 915-924.
[28] R. S. Desowitz, Plasmodium-specific immunoglobulin E in sera from an area of holoendemic malaria, Trans. R. Soc. Trop. Med. Hyg. 83(4) (1989), 478-479.
[29] L. Ding, P. S. Linsley, L. Y. Huang, R. N. Germain and E. M. Shevach, IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression, J. Immunol. 151 (1993), 1224-1234.
[30] D. L. Doolan and S. L. Hoffman, IL-12 and NK cells are required for antigen- specific adaptive immunity against malaria initiated by CD8+ T cells in the plasmodium yoelii model, J. Immunol. 163 (1999), 884-892.
[31] J. A. Dvorack, L. H. Miller, W. C. Whitehouse and T. Shiroishi, Invasion of erythrocytes by malaria merozoites, Science 187 (1975), 748-750.
[32] S. E. Farouk, T cell and antibody responses in Plasmodium falciparum malaria and their relation to disease susceptibility, Doctoral Thesis, Stockholm University, Sweden, 2005.
[33] S. E. Farouk, A. Dolo, S. Bereczky, B. Kouriba, B. Maiga, A. Farnert, H. Perlmann et al., Different antibody and cytokine-mediated responses to Plasmodium falciparum parasite in two sympatric ethnic tribes living in Mali, Microbes Infect. 7(1) (2005), 110-117.
[34] M. U. Ferreira, E. A. Kimura, A. M. Katzin, L. L. Santos-Neto, J. O. Ferrari et al., The IgG-subclass distribution of naturally acquired antibodies to Plasmodium falciparum, in relation to malaria exposure and severity, Ann. Trop. Med. Parasitol. 92 (1998), 245-256.
[35] D. F. Fiorentino, M. W. Bond and T. R. Mosmann, Two types of mouse T-helper cell. IV. Th-2 clones secrete a factor that inhibits cytokine production by Th1 clones, J. Exp. Med. 170 (1989), 2081-2095.
[36] D. F. Fiorentino, A. Zlotnik, T. R. Mosmann, M. Howard and A. Ogarra, IL-10 inhibits cytokines production by activated macrophages, J. Immunol. 147 (1991), 3815-3822.
[37] D. F. Fiorentino, A. Zlotnik, P. Vieira et al., IL-10 acts on antigen-presenting cell to inhibit cytokine production by Th1 cells, J. Immunol. 146 (1991), 3444-3451.
[38] T. F. Gajewski and F. W. Fitch, Anti-proliferation effect of IFN- in immune regulation. IFN- inhibits the proliferation of Th2 but not the murine helper T lymphocytes clones, J. Immunol. 140 (1988), 4245-4252.
[39] T. F. Gajewski, R. S. Schell, G. Nau and F. W. Fitch, Regulation of T cell activation: differences among T-cell subsets, Immunol. Rev. 111 (1989), 79-110.
[40] O. Garraud, R. Perraut, G. Riveau and T. B. Nutman, Class and subclass selection in parasite-specific antibody responses, Trends Parasitol. 19 (2003), 300-304.
[41] B. M. Gillman et al., Suppression of Plasmodium chabaudi parasitemia is independent of the action of reactive oxygen intermediates and/or nitric oxide, Infect. Immun. 72 (2004), 6359-6366.
[42] G. Giribaldi, D. Ulliers, F. Mannu, P. Arese and F. Turrini, Growth of Plasmodium falciparum induces stage-dependent haemachrome formation, oxidative aggregation of band 3, membrane deposition of complement and antibodies, and phagocytosis of parasitized erythrocytes, Br. J. Haematol. 113 (2001), 492-499.
[43] M. F. Good, Development of immunity to malaria may not be an entirely active process, Parasite Immunol. 17 (1995), 55-59.
[44] T. J. Green, M. Mordhardt, H. Groux and J. Gysin, Opsonization as an effector mechanism in human protection against asexual blood-stage of Plasmodium falciparum: functional role of IgG-subclasses, Res. Immunol. 141 (1990), 529-542.
[45] T. J. Green, M. Mordhardt, R. G. Brackett and R. L. Jacobs, Serum inhibition of merozoite dispersal from Plasmodium falciparum schizonts: indicator of immune status, Infect. Immun. 31 (1981), 1203-1208.
[46] I. W. Jones, L. L. Thomsen, R. Knowles et al., Nitric oxide synthase activity in malaria-infected mice, Parasite Immunol. 18 (1996), 535-538.
[47] L. Kabilan, M. Troye-Blomberg, M. E. Patarroyo, A. Bjorkman and P. Perlmann, Regulation of the immune response in Plasmodium falciparum malaria: IV. T cell dependent production of immunoglobulin and anti-Plasmodium falciparum antibodies in vitro, Clin. Exp. Immunol. 68 (1987), 288-297.
[48] S. Kossodo, C. Monso, P. Juillard, T. Velu, M. Goldman and G. E. Grau, Interleukin-10 modulates susceptibility in experimental cerebral malaria, Immunology 91 (1997), 536-540.
[49] J. Kuby, Immunology, W. H. Freeman & Co., Singapore, 1997.
[50] J. A. Kurtzhals, V. Adabayeri, B. Q. Goka, B. D. Akanmori, J. O. Oliver-Commey et al., Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria, Lancet 351 (1998), 1768-1772.
[51] J. R. J. Lancaster, A tutorial on the diffusibility and reactivity of free nitric oxide, Nitric Oxide 1 (1997), 18-30.
[52] J. Langhorne, S. Gillard, B. Simon, S. Slado and K. Eichmann, Frequencies of CD4+ T cells reactive with P. chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection, Int. Immunol. 1 (1989), 416-424.
[53] C. Li, I. Corraliza and J. Langhorne, A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi-chabaudi infection in mice, Infect. Immun. 67 (1999), 4435-4442.
[54] F. Liew, Y. Li, D. Moss, C. Parkinson, M. V. Rogers and S. Moncada, Resistance to Leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages, Eur. J. Immunol. 21 (1991), 3009-3014.
[55] G. Luoni, F. Verra, B. Arcà, B. S. Sirima, M. Troye-Blomberg, M. Coluzzi, D. Kwiatkowski et al., Antimalarial antibody levels and IL-4 polymorphism in the Fulani of West Africa, Genes Immun. 2 (2001), 411-414.
[56] A. J. Luty, D. J. Perkins, B. Lell, R. Schmidt-Ott, L. G. Lehman, D. Lukner, B. Greve et al., Low interleukin 12 activity in severe Plasmodium falciparum malaria, Infect. Immun. 68 (2000), 3909-3915.
[57] S. Mahanty, A. Saul and L. H. Miller, Progress in the development of recombinant and synthetic blood stage malaria vaccines, J. Exp. Biol. 206 (2003), 3781-3788.
[58] L. Malaguarnera, R. M. Imbesi, S. Pignatelli, J. Simpore, M. Malaguarnera and S. Musumeci, Increased levels of Interleukin-12 in Plasmodium falciparum malaria: correlation with severity of disease, Parasite Immunology 24 (2002), 387-389.
[59] L. H. Miller, M. Aikawa and J. A. Dvorak, Malaria (Plasmodium knowlesi) merozoites: immunity and the surface coat, J. Immunol. 114 (1975), 1237-1242.
[60] D. Modiano, V. Petrarca, B. S. Sirima, A. Bosman, I. Nebie, D. Diallo, L. Lamizana et al., Plasmodium falciparum malaria in sympatric ethnic groups of Burkina Faso, West Africa, Parasitologia 37 (1995), 255-259.
[61] D. Modiano, V. Petrarca, B. S. Sirima, I. Nebie, D. Diallo, F. Esposito and M. Coluzzi, Different responses to Plasmodium falciparum malaria in West African sympatric ethnic groups, Proc. Natl. Acad. Sci. USA 93 (1996), 13206-13211.
[62] K. W. Moore, A. O’Garra, R. De Wall Malefyt, P. Vieira and T. R. Mosmann, Interleukin 10, Ann. Rev. Immunol. 11 (1993), 165-190.
[63] K. W. Moore, P. Vieira, D. F. Fiorentino, M. L. Trounstine, T. A Khan and T. R. Mosmann, Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI, Science 248 (1990), 1230-1234.
[64] T. R. Mosmann and R. L. Coffman, Two types of mouse helper T-cell clone: implications for immune regulation, Immunol. Today 8 (1987), 223-227.
[65] T. R. Mosmann and R. L. Coffman, Th1 and Th2 cells: different patterns of lymphokine secretions lead to different functional properties, Ann. Rev. Immunol. 7 (1989), 145-173.
[66] H. Nahrevanian, Immune effector mechanisms of the NO pathway in malaria: cytotoxicity versus cytoprotection, The Brazilian Journal of Infectious Diseases 10(4) (2006), 283-292.
[67] W. Niedbala, X. Q. Wei, D. Piedrafita, D. Xu and F. Y. Liew, Effects of nitric oxide on the induction and differentiation of Th1 cells, Eur. J. Immunol. 29 (1999), 2498-2505.
[68] W. Niedbala, B. Cai and F. W. Liew, Role of nitric oxide in the regulation of T cell functions, Ann. Rheum. Dis. 65 (2006), 37-40.
[69] A. Niklas, Immune responses to repeat sequences of the Plasmodium falciparum malaria antigen Pf332, Doctoral Thesis, Stockholm University, Sweden, 1995.
[70] A. M. Nyakerga, Relation of nutritional status, immunity, hemoglobunipathy and Plasmodium falciparum malaria infection, Doctoral Thesis, Stockholm University, Sweden, 2005.
[71] A. O’Garra and N. Arai, The molecular basis of T helper 1 and T helper 2 cell differentiation, Trends Cell. Biol. 10 (2000), 542-550.
[72] C. Othoro, A. A. Lal, B. Nahlen, D. Koech, A. S. Orago and V. Udhayakumar, A low Interleukin-10/tumor necrosis factor alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya, J. Infect. Dis. 179 (1999), 279-282.
[73] D. R. Palmer and U. Krzych, Cellular and molecular requirements for the recall of IL-4 producing memory CD4+ T cells during protection induced by attenuated P. falciparum sporozoites, Eur. J. Immunol. 32 (2002), 652-661.
[74] D. J. Perkins, J. B. Weinberg and P. G. Kremsner, Reduced Interleukin-12 and transforming growth factor-1 in severe childhood malaria: relationship of cytokine balance with disease severity, J. Infect. Dis. 182 (2000), 988-992.
[75] H. Perlmann, H. Helmby, M. Hagstedt, J. Carlson, P. H. Larsson, M. Troye-Blomberg et al., IgE elevation and IgE anti-malarial antibodies in Plasmodium falciparum malaria: association of high IgE levels with cerebral malaria, Clin. Exp. Immunol. 97 (1994), 284-292.
[76] P. Perlmann, H. Perlmann, B. W. Flyg, M. Hagstedt, G. Elghazali, S. Worku, V. Fernandez et al., Immunoglobulin E, a pathogenic factor in Plasmodium falciparum malaria, Infect. Immun. 65 (1997), 116-121.
[77] P. Perlmann, H. Perlmann, S. Looareesuwan, S. Krudsood, S. Kano, Y. Matsumoto et al., Contrasting functions of IgG and IgE antimalarial antibodies in uncomplicated and severe Plasmodium falciparum malaria, Am. J. Trop. Med. Hyg. 62 (2000), 373-377.
[78] P. Perlmann and J. C. Cerottini, Cytotoxic lymphocytes, The Antigens, Vol. 5, Academic Press, Inc., New York, 1979, pp. 173.
[79] E. M. Rabin, J. J. Mond, J. Ohara and W. E. Paul, Interferon- inhibits the action of B cell stimulatory factor-1 on resting B cells, J. Immunol. 137 (1986), 1573-1576.
[80] R. Ramasamy and R. Rajakaruna, Association of malaria with inactivation of alpha1,3-galactosyl transferase in catarrhines, Biochim. Biophys. Acta 1360 (1997), 241-246.
[81] D. G. Remick and J. S. Friedland, Cytokines in Health and Disease, 2nd Review and Expand Edition, Marcel Decker, New York, 1997.
[82] D. Salmon, J. L. Vilde, B. Andrieu, R. Simonovic and J. Lebras, Role of immune serum and complement in stimulation of the metabolic burst of human neutrophils by Plasmodium falciparum, Infect. Immun. 51 (1986), 801-806.
[83] L. A. Sanni, W. Jarra, C. Li and J. Langhorne, Cerebral malaria and cerebral hemorrhages in Interleukin-10-deficient mice infected with Plasmodium chabaudi, Infect. Immun. 72 (2004), 3054-3058.
[84] J. Schmitz, M. Assenmacher and A. Radbruch, Regulation of T-helper cytokine expression: functional dichotomy of antigen presenting cells, Eur. J. Immunol. 23 (1993), 191-199.
[85] M. Sedegah, F. Finkelman and S. L. Hoffman, Interleukin-12 induction of interferon-gamma dependent protection against malaria, Proc. Natl. Acad. Sci. USA 91(22) (1994), 10700-10702.
[86] R. A. Seder and W. E. Paul, Acquisition of lymphokine-producing phenotype by CD4+ T cells, Annu. Rev. Immunol. 12 (1994), 635-673.
[87] P. Sobolewski, I. Gramaglia, J. Frangos et al., Nitric oxide bioavailability in malaria, Trends in Parasitology 21(9) (2005a), 2499-2505.
[88] P. Sobolewski, I. Gramaglia, A. J. Frangos, M. Intaglietta and H. van der Heyde, Plasmodium Berghei resist killing by reactive oxygen species, Infection and Immunity 73(10) (2005b), 6704-6710.
[89] H. L. Spiegelberg, Biological activities of immunoglobulins of different classes and subclasses, Adv. Immunol. 19 (1974), 259-294.
[90] M. M. Stevenson et al., Innate immunity to malaria, Nat. Rev. Immunol. 4 (2004), 169-180.
[91] Z. Su and M. M. Stevenson, IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice, J. Immunol. 168 (2002), 1348-1355.
[92] G. Suss and J. R. Pink, A recombinant malaria protein that can induce Th1 and CD8+ T cell responses without antibody formation, J. Immunol. 149 (1992), 1334-1339.
[93] A. W. Taylor-Robinson and M. Looker, Sensitivity of malaria parasites to nitric oxide at low oxygen tensions, Lancet 351 (1998), 1630.
[94] A. W. Taylor-Robinson, Immunoregulation of malarial infection: balancing the vices and virtues, International Journal for Parasitology 28 (1998), 135-148.
[95] A. W. Taylor-Robinson, Nitric oxide can be released as well as scavenged by hemoglobin: relevance to its antimalarial activity, Parasite Immunol. 20 (1998b), 49-50.
[96] A. W. Taylor-Robinson, R. S. Phillips, A. Severn, S. Moncada and F. Y. Liew, The role of Th1 and Th2 cells in a rodent malaria infection, Science 260 (1993), 1931-1934.
[97] A. W. Taylor-Robinson and R. S. Phillips, Functional characterisation of protective CD4+ T-cell clones reactive to the murine malaria parasite Plasmodium chabaudi, Immunology 77 (1992), 99-105.
[98] A. W. Taylor-Robinson, Regulation of immunity to malaria: valuable lessons learned from murine models, Parasitol. Today 11(9) (1995), 334-342.
[99] A. W. Taylor-Robinson, Counter-regulation of T helper 1 cell proliferation by nitric oxide and IL-2, Biochem. Biophys. Res. Commun. 233 (1997), 14-19.
[100] A. E. Tebo, P. G. Kremsner and A. J. Luty, Plasmodium falciparum: a major role for IgG3 in antibody-dependent monocyte-mediated cellular inhibition of parasite growth in vitro, Exp. Parasitol. 98 (2001), 20-28.
[101] P. Thuma and G. Weiss, Markers of inflammation in children with severe malaria anemia, Trop. Med. Int. Health 5(4) (2000), 256-262.
[102] D. Torre, F. Speranza, M. Giola, A. Matteelli, R. Tambini and G. Bioni, Role of Th1 and Th2 cytokines in immune response to uncomplicated Plasmodium falciparum malaria, Clinical and Diagnostic Laboratory Immunology 9(2) (2002), 348-351.
[103] G. Trinchieri, Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen specific adaptative immunity, Ann. Rev. Immunol. 12 (1995), 251-276.
[104] G. Trinchieri, Interleukin-12 and its role in the generation of Th1 cells, Immunol. Today 14 (1993), 335-338.
[105] M. Troye-Blomberg and P. Perlmann, Malaria immunity: an overview with emphasis on T cell functions, Molecular Immunological Considerations in Malaria Vaccine Development, M. F. Good and A. J. Saul, ed., CRC Press Inc., Boca Raton, 1994, pp. 1-46.
[106] N. Tuteja et al., Nitric oxide as a unique bioactive signalling messenger in physiology and pathophysiology, J. Biomed. Biotechnol. 2004(4) (2004), 227-237.
[107] I. J. Udeinya, L. H. Miller, I. A. McGregor and J. B. Jensen, Plasmodium falciparum strain-specific-antibody blocks binding of infected erythrocytes to amelanotic melanoma cells, Nature 303 (1983), 429-431.
[108] R. C. Van der Veen, Nitric oxide and T helper cell immunity, Int. Immunopharmacol. 1 (2001), 1491-1500.
[109] F. Verra, G. Luoni, C. Calissano, M. Troye-Blomberg, P. Perlmann et al., IL4-589 C/T polymorphism and IgE levels in severe malaria, Acta Tropica 90 (2004), 205-209.
[110] T. Von der Weid and J. Langhorne, The roles of cytokines produce in the immune response to the erythrocytic stages of mouse malarias, Immunobiology 189 (1993), 397-418.
[111] M. Wahlgren, K. Berzins, P. Perlmann and M. Persson, Characterisation of the humoral immune response in Plasmodium falciparum malaria. II. IgG subclass levels of anti-Plasmodium falciparum antibodies in different sera, Clin. Exp. Immunol. 54 (1983), 135-142.
[112] B. Wahlin, M. Wahlgren, H. Perlmann, K. Berzins, A. Bjorkman, M. Patarroyo and P. Perlmann, Human antibodies to a Mr 155,000 Plasmodium falciparum antigen efficiently inhibit merozoite invasion, Proc. Natl. Acad. Sci USA 81 (1984), 7912-7916.
[113] J. N. Wilson, K. Rockett, M. Jallow, M. Pinder, F. Sisay-Joof et al., Analysis of IL-10 haplotypic associations with severe malaria, Genes Immun. 6 (2005), 462-466.
[114] A. Windhagen, D. E. Anderson, A. Carrizosa, R. E. Williams and D. A. Hafler, IL-12 induces human T cells secreting IL-10 with IFN-, J. Immunol. 157 (1996), 1127-1131.
[115] S. Winkler, M. Willheim, K. Baier, D. Schmid, A. Aichelburg, W. Graninger and P. G. Kremsner, Reciprocal regulation of Th1- and Th2-cytokine producing T cells during clearance of parasitemia in Plasmodium falciparum malaria, Infection and Immunity 66(12) (1998), 6040-6044.
[116] J. B. De Souza, K. H. Williamson, T. Otani and J. H. Playfair, Early gamma interferon responses in lethal and nonlethal murine blood-stage malaria, Infect. Immun. 65(5) (1997), 1593-1598.
[117] K. Artavanis-Tsakonas and E. M. Riley, Innate immune response to malaria: rapid induction of IFN-gamma from human NK cells by live Plasmodium falciparum-infected erythrocytes, J. Immunol. 169(6) (2002), 2956-2963.
[118] L. Hviid, J. A. Kurtzhals, V. Adabayeri, S. Loizon, K. Kemp, B. Q. Goka et al., Perturbation and proinflammatory type activation of V delta 1(+) gamma delta T cells in African children with Plasmodium falciparum malaria, Infect. Immun. 69(5) (2001), 3190-3196.
[119] S. Pied, J. Roland, A. Louise, D. Voegtle, V. Soulard, D. Mazier et al., Liver CD4-CD8-NK1.1+TCR alpha beta intermediate cells increase during experimental malaria infection and are able to exhibit inhibitory activity against the parasite liver stage in vitro, J. Immunol. 164(3) (2000), 1463-1469.
[120] M. C. D’Ombrain, L. J. Robinson, D. I. Stanisic, J. Taraika, N. Bernard, P. Michon et al., Association of early interferon-gamma production with immunity to clinical malaria: a longitudinal study among Papua New Guinean children, Clin. Infect. Dis. 47(11) (2008), 1380-1387.
[121] M. B. B. McCall, J. Hopman, M. Daou, B. Maiga, V. Dara, I. Ploemen et al., Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali, J. Infect. Dis. 201(1) (2010), 142-152.