Suzuki Y, Joh K, Orellana M A, Conley F K, Remington J S
Department of Parasitology, Jikei University School of Medicine, Tokyo, Japan.
Immunology. 1991 Dec;74(4):732-9.
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.
在小鼠模型中进行了研究，以确定弓形虫性脑炎的发展是否受遗传控制。用刚地弓形虫ME49株感染10周后，具有H-2b单倍型（C57BL/6、C57BL/10）和H-2k单倍型（C3H/He、CBA/J）的小鼠大脑出现了明显的炎症变化，而具有H-2a单倍型（A/J）和H-2d单倍型（BALB/c、DBA/2）的小鼠则没有。在具有H-2b和H-2k单倍型的小鼠急性局灶性炎症区域，通过免疫过氧化物酶染色证实了速殖子和弓形虫抗原的存在，这表明局灶性炎症是由弓形虫生物体诱导的。B10同源基因小鼠用于进一步分析这种遗传调控。感染后10周，B10和B10.BR小鼠出现脑炎，而B10.A和B10.D2小鼠未出现，这表明H-2复合体内的一个基因对炎症有调控作用。感染期间，B10.A（2R）和B10.A（4R）小鼠出现脑炎，而B10.A（3R）和B10.A（18R）小鼠未出现。这些结果清楚地表明，弓形虫性脑炎的发展受H-2D区域的一个基因控制。Qa和Tla基因在确定对脑炎的易感性方面似乎并不关键。血清弓形虫抗体滴度与脑炎的发生之间没有相关性。注射抗γ干扰素（IFN-γ）单克隆抗体显著增强了感染的B10小鼠大脑中的炎症变化。相比之下，该处理在感染的BALB/c小鼠大脑中未诱导任何炎症反应。类似的遗传调控可能在确定艾滋病和其他免疫受损患者的弓形虫性脑炎发展中起作用。
