Abstract
IFN-γ receptor-deficient (IFN-γR−/−) mice and control wild-type (WT) mice, with or without chloroquine (CQ) treatment, were infected intraperitoneally with Plasmodium yoelii 17XL (lethal) and P. yoelii 17XNL (nonlethal), and then mouse survival, parasitemia, and antibody production were investigated during the course of infection. Without CQ treatment, both IFN-γR−/− and WT mice were susceptible to infection showing 100 % mortality after infection with 1 × 105 P. yoelii 17XL-parasitized erythrocytes. The P. yoelii 17XL-infected WT mice could survive by CQ treatment at a dose of 20 mg/kg for 3 days from day 3 postinfection (pi). Malaria parasites in their bloodstream could not be detected in the surviving mice after day 13 pi. CQ treatment, however, could not rescue IFN-γR−/− mice infected with P. yoelii 17XL. Next, we examined the production of the parasite-specific antibodies in P. yoelii 17XL-infected, CQ-treated mice. Although the production of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies was observed on days 14 and 28 pi in WT mouse sera, only IgG1 was detected on day 28 pi in IFN-γR−/− mouse sera. On the other hand, in the nonlethal P. yoelii 17XNL infection, WT mice could control a primary infection with 1 × 105 parasitized erythrocytes. Although IFN-γR−/− mice could not control and died with increasing parasitemia, the mice could survive by CQ treatment. Both WT and IFN-γR−/− mice with and without medication, which survived from P. yoelii 17XNL infection, showed the variable levels of malaria-specific IgG1, IgG2a, IgG2b, and IgG3 antibodies during the course of infection. The present data indicate that the IFN-γ receptors are needed to control the infection and parasite-specific IgG2a antibody plays an essential role in recovery from the infection of erythrocytic stages of P. yoelii 17XL or P. yoelii 17XNL parasite.
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References
Chang K-H, Stevenson MM (2004) Malarial anaemia: mechanisms and implications of insufficient erythropoiesis during blood-stage malaria. Int J Parasitol 34:1501–1516
Dalton DK, Pitts-Meek S, Keshav S, Figari IS, Bradley A, Stewart TA (1993) Multiple defects of immune cell function in mice with disrupted interferon-γ genes. Science 259:1739–1742
Favre N, Ryffel B, Bordmann G, Rudin W (1997) The course of Plasmodium chabaudi chabaudi infections in interferon-gamma receptor deficient mice. Parasite Immunol 19:375–383
Goldman IF, Qari SH, Skinner J, Oliveira S, Nascimento JM, Povoa MM, Collins WE, Lal AA (1992) Use of glass beads and CF11 cellulose for removal of leukocytes from malaria-infected human blood in field settings. Mem Inst Oswaldo Cruz 87:583–587
Griffith JW, O’Connor C, Bernard K, Town T, Goldstein DR, Bucala R (2007) Toll-like receptor modulation of murine cerebral malaria is dependent on the genetic background of the host. J Infect Dis 196:1553–1564
Huang S, Hendriks W, Althage A, Hemmi S, Bluethmann H, Kamijo R, Vilcek J, Zinkernagel RM, Aguet M (1993) Immune response in mice that lack the interferon-γ receptor. Science 259:1742–1745
Ishih A, Nagata T, Kobayashi F, Miyase T, Terada M (2004) Cytokine and antibody production during the course of resolution in Plasmodium yoelii 17XL-infected BALB/c mice treated with febrifugine and isofebrifugine mixture from leaves of Hydrangea macrophylla var. Otaksa. Parasitol Res 94:176–182
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 64:44–49
Langhorne J, Gillard S, Simon B, Slade S, Eichmann K (1989) Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. Int Immunol 1:416–424
Li C, Seixas E, Langhorne J (2001) Rodent malarias: the mouse as a model for understanding immune responses and pathology induced by the erythrocytic stages of the parasite. Med Microbiol Immunol 189:115–126
Matsumoto S, Yukitake H, Kanbara H, Yamada H, Kitamura A, Yamada T (2001) Mycobacterium bovis bacillus Calmette-Guerin induces protective immunity against infection by Plasmodium yoelii at blood-stage depending on shifting immunity toward Th1 type and inducing protective IgG2a after the parasite infection. Vaccine 19:779–787
Otsuki H, Kaneko O, Thongkukiatkul A, Tachibana M, Iriko H, Takeo S, Tsuboi T, Torii M (2009) Single amino acid substitution in Plasmodium yoelii erythrocytic ligand determinants its location and controls parasite virulence. Proc Natl Acad Sci U S A 106:7167–7172
Pattaradilokrat S, Cheesman SJ, Carter R (2008) Congenicity and genetic polymorphism in cloned lines derived from a single isolate of a rodent malaria parasite. Mol Biochem Parasitol 157:244–247
Playfair JH, De Souza JB, Cottrell BJ (1977) Protection of mice against malaria by a killed vaccine: differences in effectiveness against P. yoelii and P. berghei. Immunol 33:507–515
Rosa R, Silveira H, Seixas E, Rolao N, Santos-Gomes G, do Rosario V (1999) The effect of chloroquine on the production of interferon-γ, interleukin (IL)-4, IL-6, and IL-10 in Plasmodium chabaudi chabaudi in infected C57BL6 mice. J Parasitol 85:956–960
Shear HL, Srinivasan R, Nolan T, Ng C (1989) Role of IFN-γ in lethal and non lethal malaria in susceptible and resistant murine hosts. J Immunol 143:2038–2044
Shibui A, Hozumi N, Shiraishi C, Sato Y, Iida H, Sugano S, Watanabe J (2009) CD4+ T cell response in early erythrocytic stage malaria: Plasmodium berghei infection in BALB/c and C57BL/6 mice. Parasitol Res 105:281–286
Smith EC, Taylor-Robinson AW (2003) Parasite-specific immunoglobulin isotypes during lethal and non-lethal murine malaria infections. Parasitol Res 89:26–33
Stevenson MM, Riley EM (2004) Innate immunity to malaria. Nat Rev 4:169–180
Stevenson MM, Tam M-F (1993) Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin Exp Immunol 92:77–83
Stevenson MM, Tam MF, Belosevic M, van der Meide PH, Podoba JE (1990) Role of endogeneous gamma interferon in host response to infection with blood-stage Plasmodium chanadi AS. Infect Immun 58:3225–3232
Taylor DW, Pacheco E, Evan’s CB, Asofsky R (1988) Inbred mice infected with Plasmodium yoelii differ in their antimalarial immunoglobulin isotype response. Parasite Immunol 10:33–46
Taylor-Robinson AW (2010) Regulation of immunity to Plasmodium: implications from mouse models for blood stage malaria vaccine design. Exp Parasitol 126:406–414
Tsuji M, Miyahira Y, Nussenzweig RS, Aguet M, Reichel M, Zavala F (1995) Development of antimalarial immunity in mice lacking IFN-γ receptor. J Immunol 154:5338–5344
von der Weid T, Langhorne J (1993) The role of cytokines produced in the immune response to the erythrocytic stages of mouse malarias. Immunobiology 89:397–418
Waki S, Uehara S, Kanbe K, Ono K, Suzuki M, Nariuchi H (1992) The role of T cells in pathogenesis and protective immunity to murine malaria. Immunology 75:646–651
White WI, Evans BE, Taylor DW (1991) Antimalarial antibodies of the immunoglobulin G2a isotype modulate parasitemias in mice infected with Plasmodium yoelii. Infect Immun 59:3547–3554
Yoeli M, Hargreaves B, Carter R, Walliker D (1975) Sudden increase in virulence in a strain of Plasmodium berghei yoelii. Ann Trop Med Parasitol 69:173–178
Yoshida A, Nagata T, Uchijima M, Koide Y (2001) Protective CTL response is induced in the absence of CD4+ T cells and IFN-γ by gene gun DNA vaccination with a minigene encoding a CTL epitope of Listeria monocytogenes. Vaccine 19:4297–4306
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Ishih, A., Kawakami, C., Todoroki, A. et al. Outcome of primary lethal and nonlethal Plasmodium yoelii malaria infection in BALB/c and IFN-γ receptor-deficient mice following chloroquine treatment. Parasitol Res 112, 773–780 (2013). https://doi.org/10.1007/s00436-012-3197-y
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DOI: https://doi.org/10.1007/s00436-012-3197-y