Immunogenetics in pathogenesis of and protection against toxoplasmosis.

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et al. 1984, 1988; Suzuki et al. 1989; Sibley and Boothroyd 1992; Suzuki and Joh 1994), inoculum size (Johnson et al., unpublished), host age (Johnson et al. unpublished), sex hormones (Roberts et al. 1995), and immune status (Gazzinelli et al. 1993a,b) also clearly modulate and effect outcome of infection.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).