Abstract
Clinical manifestations and congenital transmission rates vary markedly among individuals with Toxoplasma infection (reviewed in Boyer and McLeod 1996; Remington et al. 1995). An influence of host immune response genes on the outcome of congenital infection is supported by observations of concordance of manifestations in monozygotic versus discordance of manifestations in dizygotic twins (Couvreur et al. 1976; reviewed in Remington et al. 1995), ethnic variations in incidence and severity of manifestations of disease (McAuley et al. 1994) and recent HLA typing studies (Mack et al. 1996b). Data from studies of murine models indicate that variables such as parasite strain (McLeod et al. 1984, 1988; Suzuki et al. 1989; Sibley and Boothroyd 1992; Suzuki and Joh 1994), inoculum size (Johnson et al., unpublished), host age (Johnson et al. unpublished), sex hormones (Roberts et al. 1995), and immune status (Gazzinelli et al. 1993a,b) also clearly modulate and effect outcome of infection. Studies are under way to define precisely how host genetics, as well as certain of the variables mentioned above, determine the small proportion of immunologically competent older children and adults who develop various disease manifestations. These studies are focused on the role of genetics in determining disease manifestations such as those described in systemic (reviewed in Boyer and McLeod 1996), retinal (Couvreur and Thulliez 1996), neurologic disease (Townsend et al. 1975), or lymphadenopathic toxoplasmosis (McCabe et al. 1987; Montoya and Remington 1995). In addition, these studies address whether immunogenetics influence the small proportion of acutely infected women who transmit infection to their fetuses early in gestation (Hohfeld et al. 1994), the 40% of T. gondii seropositive patients with AIDS who develop toxoplasmic encephalitis (Luft and Remington 1992), the severity of manifestations of congenital infection (McAuley et al. 1994; Mack et al. 1996b) or the occurrence or frequency of episodes of reactivation in recurrent retinochoroiditis in individuals with toxoplasmic retinochoroiditis (Mets et al. 1992; Mets et al. 1996).
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References
Abbas AK, Lichtman AH, Pober JS (1991) Cellular and molecular immunology. Saunders, Philadelphia
Aosai F, Yang TH, Ueda M, Yano A (1994): Isolation of naturally processed peptides from a Toxoplasma gondii-infected human B lymphoma cell line that are recognized by cytotoxic T lymphocytes. J Parasitol 80:260–266
Beaman MH, Araujo FG, Remington JS (1994) Protective reconstitution of the SCID mouse against reactivation of toxoplasmic encephalitis. J Infect Dis 160:375–383
Blackwell J, Roberts CW, Alexander J (1993) Influence of genes within the MHC on mortality and brain cyst development in mice infected with Toxoplasma gondii: kinetics of immune regulation in BALB H-2 congenic mice. Parasite Immun 15:317–324
Blackwell JM, Roberts CW, Roach TI, Alexander J (1994) Inlluence of macrophage resistance gene LSH/ITy/Bcg (candidate NRamp on Toxoplasma gondii infection in mice). Clin Exp Immunol 97:107–112
Bodner JG, Marsh SGE, Albert ED, Bodmer WF, Dupont B, Erlich HD, Mach B, Mayr WR, Patnam P, Sasazuld T (1994) Nomenclature report: nomenclature lor lactors of the HLA system. Tissue Antigens 44:1–18
Bohne W, Heesemann J, Gross U (1994) Reduced replication of Toxoplasma gondii is necessary lor induction of bradyzoite-specilic antigens: a possible role lor nitric oxide in triggering stage conversion. Infect Immun 62: 1761–1767
Boyer K, McLeod R (1996) Toxoplasma gondii and Toxoplasmosis. In: Long S, Proeber C, Pickering, L (eds) Pediatric infectious diseases. Churchill Livingstone (in press)
Brown CR, McLeod R (1990) Class I MHC genes and CD8+ T cells determine cyst number in Toxoplasma gondii infection. J Immunol 145:3438–3441
Brown CR, McLeod R (1994) Mechanisms of survival of mice during acute and chronic T. gondii infection. Parasitol Today 10:290–292
Brown C, David C, Kahn SJ, McLeod R (1994) Effect of human MHC class I genes on outcome of T. gondii cyst formation. J Immunol 152:4537–4541
Brown CR, Hunter C, Estes R, Beckmann E, Forman J, David C, Remington JS, McLeod R... (1995) Delinitive identilication of a gene that conlers resistance against toxoplasmosis. Immunology 85:419–429
Burke JM, Roberts CW, Hunter CA, Murray M, Alexander J (1994) Temporal differences in the expression of mRNA lor IL-10 and IFN-γ in the brains and spleens of C57BL/10 mice infected with Toxoplasma gondii. Parasite Immunol 15:305–314
Couvreur J, Desmonts G, Girre JY (1976) Congenital toxoplasmosis in twins. J Ped 69:235–240
Couvreur J, Thulliez P (1996) Toxoplasmose acquise a localisation oculaire ou neurologique — 49 cas. Presse Med 25:438–442
Deckert-Schlüter, Albrecht S, Hol H, Wiestier OD, Schlüter D (1995) Dynamics of the intracerebral and splenic mRNA production in Toxoplasma gondii-resistant and-susceptible congenic strains of mice. Immunology 85:408–419
Denkers E, Gazzinelli R, Martin D, Sher A (1993) Emergence of NK1,1+ cells as effectors of IFN-γ dependent immunity to Toxoplasma gondii in MHC class I deficient mice. J Exp Med 175:1465–1472
Denkers EY, Casper P, Sher A (1994) Toxoplasma gondii possesses a superantigen activity that selectively expands murine T cell receptor V ß 5 bearing CD8+ lymphocytes. J Exp Med 180:985–994
Gazzinelli RT, Oswald IP, James SL, Sher A (1992) IL-10 inhibits parasite killing and nitrogen oxide production by IFN-γ activated macrophages. J Immunol 148: 1792–1796
Gazzinelli RT, Denkers EY, Sher A (1993a) Host resistance to Toxoplasma gondii, a model lor studying the selective induction of cell-mediated immunity by intracellular parasites. Infect Agents Dis 2139-149
Gazzinelli RT, Eltoum I, Wynn TA, Sher A (1993b) Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-± and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol 151:3672–3681
Gazzinelli RT, Wysocka M, Hayashi S, Denkers EY, Hieny S, Casper P, Trinchieri G, Sher A (1994) Parasite-induced IL-12 stimulates early IFN-γ synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol 153:2533–2543
Gazzinelli RT, Wysocka M, Hieny S, Kersten T, Carrera L, Cheever A, Kühn R, Müller W, Trinchieri G, Sher A (1996) In the absence of endogenous IL-10 mice acutely inlected with Toxoplasma gondii succumb to alethal immune response associated with increased synthesis of IL-12, IFN-γ and TNF-α. J. Immunol. (in press)
Hili AVS, Elvin J, Willis AC, Aidoo M, Allsopp CE, Gotch FM, Gai XM, Takiguchi M, Greenwood BM, Townsend AR (1992) Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360:434–439
Hohfeld P, Daffos F, Costa JM, Thulliez P, Forestier F, Vidaud M (1994) Prenatal diagnosis of congenital toxoplasmosis with a polymerase-chain reaction test on amniotic fluid. N Engl J Med 331:695–699
Hunt DF, Henderson RA, Shabanowitz J, Sakaguchi K, Michel H, Sevilir N, Cox AL, Apella E, Engelhard VH (1992) Characterization of peptides bound to the class I MHC molecule HLA-A2 by mass spectrometry. Science 255: 1261–1263
Hunter CA, Subauste CS, Van Cleave VH, Remington JS (1994) Production of IFN-γ by natural killer cells from Toxoplasma gondii-infected SCID mice: regulation by interleukin-10, interleukin-12, and tumor necrosis factor-α. Infect Immun 62:2818–2824
Jones TC, Erb P (1985) H-2 Complex-linked resistance in murine toxoplasmosis. J Inf Dis 151:739–740
Johnson LL (1994) Resistanee to Toxoplasma gondii in mice infected as neonates or exposed in utero. Infect Immun 62:3075–3079
Kaufmann SHE (1994) Bacterial and protozoal infections in genetieally disrupted mice. Curr Opin Immunol 5:518–525
Khan IA, Matsuura T, Kasper LH (1994) Interleukin-12 enhances murine survival against acute toxoplasmosis. Infect Immun 62: 1639–1642
Luft BJ, Remington JS (1992) Toxoplasmic eneephalitis in AIDS. Clin Inf Dis 15:211–222
Lukachar AE, Yupo M, Carroll JP, Abromson-Leeman SR, Laning C, Darf ME, Benjamin T (1995) Susceptibility to tumors indueed by polyoma virus is eonferred by an endogenous mouse mammary tumor virus superantigen. J Exp Med 151:1683–1692
Mack D, Estes RG, McLeod R (1996a) Toxoplasma gondii superantigen (manuscript in preparation)
Mack D, Johnson J, Estes R, David C, Grumet C, Terasaki P, McLeod R (1996b) Toxoplasmosis suseeptibility genes (manuseript in preparation)
Marraek P, Kappier J (1994) Subversion of the immune system by pathogens. Cell 76:323–332
Marrack P, Kushnir E, Kappier J (1991) A naturally inherited superantigen encoded bya mammary tumour virus. Nature 349:524–526
McAuley J, Boyer K, Patel D, Mets M, Swisher C, Roizen N, Wolters C, Stein L, Stein M, Schey W, McLeod R (1994) Early and longitudinal evaluations of treated infants and children and untreated historical patients with congenital toxoplasmosis: the Chieago collaborative treatment trial. Clin Inf Dis 18:38–72
McCabe RE, Brooks RG, Dorfman RF, Remington JS (1987) Clinical speetrum in 107 cases of toxoplasmie Iymphadenopathy. Rev Infect Dis 9:754–774
McLeod R, Cohen H, Estes R (1984) Immune response to ingested Toxoplasma: deseription of a mouse model of Toxoplasma acquired by ingestion. J Infect Dis 149:234–244
McLeod R, Frenkel JK, Estes RG, Maek DG, Eisenhauer P, Gibori G (1988) Subeutaneous and intestinal vaccination with tachyzoites of Toxoplasma gondii and acquisition of immunity to peroral and congenital Toxoplasma ehallenge. J Immunol 140:1632–1637
McLeod R, Eisenhauer P, Mack DG, Filice G, Spitalny G (1989a) Immune responses associated with early survival after peroral infection with Toxoplasma gondii. J. Immunol 142:3247–3255
McLeod R, Skamene E, Brown CR, Eisenhauer P, Mack D (1989b) Genetic regulation of early survival and cyst number after peroral Toxoplasma gondii infection ofAXB/BXA recombinant inbred and B10 congenic mice. J Immunol 143:3031–3034
McLeod R, Maek DG, Brown C, Skamene E (1993a) Secretory IgA antibody to SAG 1, H-2 class I restrieted CD8+ T-Iymphoeytes and the INT-1 loeus in proteetion against Toxoplasma gondii. In: Smith J (ed) Toxoplasmosis. NATO ASI Series H. Cell Biology; vol. 78. Springer, Berlin, Heidelberg, New York, pp 131–151
McLeod R, Brown C, Mack D (1993b) Immunogenetics influence outcome of T. gondii infeetion. Res Immunol Ann Inst Pasteur 144:61–66
McLeod R, Bushman E, Arbuckle D, Skamene E (1995) Immunogeneties in the analysis of resistanee to intraeellular pathogens. Curr Opin Immunol 7:539–552
Mets M, Holfels E, McLeod R, and the Toxoplasmosis Study Group (1992) Ophthalmologic findings in congenital toxoplasmosis. Invest Ophthal Vis Sci 33:4
Mets M, Holfels E, McLeod R, and the Toxoplasmosis Study Group (1996) The eye manifestations of toxoplasmosis. Am J Ophthalmol (in press)
Miyahira Y, Murata K, Rodriguez D, Rodriguez JR, Esteban M, Rodrigues M, Zavala F (1995) Quantification of antigen specific CD8+ T cells using an ELLISPOT assay. J Immunol Method 181:45–54
Montoya G, Remington J (1995) Studies on the serodiagnosis of toxoplasmic lymphadenitis. Clin Inf Dis 20:781–789
Nadeau JH, Arbuckle LD, Skamene E (1995) Genetic dissection of inflammatory responses. J Inflamm 45:27–48
Paigen K (1995) A miracle enough: the power of mice. Nature Med 1:215–220
Pamer EG, Harty JT, Bevan PNJ (1991) Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes. Nature 353:852–855
Remington JS, McLeod R, Desmonts G (1995) Congenital Toxoplasmosis. In: Remington JS, Klein J (eds) Infections of the fetus and newborn infant. Saunders, Philadelphia, 140–268
Roberts CW, Cruickshank SM, Alexander J (1995) Sex determined resistance to Toxoplasma gondii is associated with temporal differences in cytokine production. Infect Immun 63:2549–2555
Roberts CW, Ferguson DJP, Jebbari H, Satoskar A, Bluethmann H, Alexander J (1996) Different roles for IL4 during the course of Toxoplasma gondii infection. Infect Immun 64:897–904
Sher A, Oswald IP, Hieny S, Gazzinelli RT (1993) Toxoplasma gondii induces a T-independent IFN-γ response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-α. J Immunol 150:3982–3989
Sibley DL, Adams LB, Fukutomi Y, Krahenbuhl JL (1991) Tumor necrosis factor-± triggers antitoxoplasmal activity of IFN-γ primed macrophages. J Immunol 147:2340–2345
Sibley DL, Boothroyd J (1992) Virulent strains of Toxoplasma gondii comprise a single clonal lineage. Nature 359:82–85
Suzuki Y, Joh K (1994) Effect of the strain of Toxoplasma gondii on the development of toxoplasmic encephalitis in mice treated with antibody to IFN-γ. Parasitol Res 80: 125–130
Suzuki Y, Remington JS (1993) Susceptibility to chronic infection with Toxoplasma gondii does not correlate with susceptibility to acute infection. Infect Immun 61:2264–2288.
Suzuki Y, Conley F, Remington JS (1989) Differences in virulence and development of encephalitis during chronic infection vary with the strain of Toxoplasma gondii. J Infec Dis 159:790–793
Suzuki Y, John K, Orellana MA, Conley FK, Remington JS (1991) A gene(s) within the H-2D region determines the development of toxoplasmic encephalitis in mice. Immunology 74:732–739
Suzuki Y, Joh K, Kwon OC, Yang Q, Conley FK, Remington JS (1994) MHC class I gene(s) in the D/L region but not the TNF-± gene determines development of toxoplasmic encephalitis in mice. J Immun 97:4649–4654
Townsend JJ, Wolinsky JS, Barringer JR, Johnson PC (1975) Acquired toxoplasmosis. Arch Neurol 32:335–343
Williams DM, Grumet FC, Remington JS (1978) Genetic control of murine resistance to Toxoplasma gondii. Infect Immun 9:416–420
Zanelli E, Gonzalez-Gay MA, David CS (1995) Could HLA-DRI be the protective locus in rheumatoid arthritis? Immunol Today 16:274–278
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McLeod, R., Johnson, J., Estes, R., Mack, D. (1996). Immunogenetics in Pathogenesis of and Protection Against Toxoplasmosis. In: Gross, U. (eds) Toxoplasma gondii. Current Topics in Microbiology and Immunology, vol 219. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-51014-4_10
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DOI: https://doi.org/10.1007/978-3-642-51014-4_10
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