A gene(s) within the H-2D region determines the development of toxoplasmic encephalitis in mice.
Studies were performed in a murine model to determine if there is genetic control of the development of toxoplasmic encephalitis. Ten weeks after infection with the ME49 strain of Toxoplasma gondii, mice with the H-2b haplotype (C57BL/6, C57BL/10) and H-2k haplotype (C3H/He, CBA/J) developed remarkable inflammatory changes in their brains, whereas mice with the H-2a haplotype (A/J) and H-2d haplotype (BALB/c, DBA/2) did not. In the area of acute focal inflammation in mice with the H-2b and H-2k haplotypes, tachyzoites and toxoplasma antigens were demonstrated by immunoperoxidase staining, suggesting that the focal inflammation was induced by toxoplasma organisms. B10 congenic mice were used for further analysis of this genetic regulation. Presence of the encephalitis in B10 and B10.BR but not in B10.A and B10.D2 mice at 10 weeks after infection indicated regulation of the inflammation by a gene(s) within the H-2 complex. The encephalitis developed in B10.A (2R) and B10.A (4R) mice but not in B10.A (3R) and B10.A (18R) during infection. These results clearly indicated that the development of toxoplasmic encephalitis was controlled by a gene(s) in the H-2D region. The Qa and Tla genes did not appear to be critical in determining susceptibility to the encephalitis. There was no correlation between serum toxoplasma antibody titres and occurrence of the encephalitis. Injection of a monoclonal antibody to interferon-gamma (IFN-gamma) remarkably augmented the inflammatory changes in the brains of the infected B10 mice. In contrast, the treatment did not induce any inflammatory response in the brains of the infected BALB/c mice. A similar genetic regulation may be operative in determining development of toxoplasmic encephalitis in AIDS and other immunocompromised patients.
Suzuki
Y
Y
Department of Parasitology, Jikei University School of Medicine, Tokyo, Japan.
Joh
K
K
Orellana
M A
MA
Conley
F K
FK
Remington
J S
JS
D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis; D001921:Brain / Q000473:pathology; D004660:Encephalitis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000235:genetics* / Q000473:pathology; D016781:Toxoplasmosis, Cerebral / Q000235:genetics* / Q000473:pathology
D000913:Antibodies, Protozoan; D007371:Interferon-gamma