Suzuki Y, Yang Q, Yang S, Nguyen N, Lim S, Liesenfeld O, Kojima T, Remington J S
Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, CA 94301.
J Immunol. 1996 Sep 15;157(6):2564-9.
IFN-gamma is critical for prevention of development of toxoplasmic encephalitis (TE). Since IL-4 down-regulates production of IFN-gamma, we examined its role in the pathogenesis of TE in IL-4-targeted mutant (IL-4-/-) mice. IL-4-/- mice all died from 6 to 20 wk after peroral infection with cysts of the ME49 strain of Toxoplasma gondii; control mice survived. At 4 and 8 wk after infection, significantly greater numbers of T. gondii cysts and foci of acute inflammation, and greater amounts of tachyzoite-specific mRNA (by reverse-transcriptase PCR) were in brains of IL-4-/- mice than controls. Toxoplasma IgG2b and IgG3 Ab levels were slightly but significantly higher in sera of IL-4-/- than control mice, whereas IgM and IgG2a levels did not differ between these mice. Toxoplasma IgG1 and IgE Abs were not detected in sera of either strain. Amounts of IFN-gamma, TNF-alpha, IL-6, and IL-10 mRNA detected by reverse-transcriptase PCR did not differ between brains of infected IL-4-/- and controls, although brains of the former mice had greater numbers of inflammatory mononuclear cell infiltrates. IL-4 mRNA was detected only in infected control mice. Spleen cells of control mice at 8 wk after infection produced significantly greater amounts of IFN-gamma following stimulation in vitro with soluble T. gondii Ags than did those from IL-4-/- mice. These results indicate that IL-4 is protective against development of TE by preventing formation of T. gondii cysts and proliferation of tachyzoites in the brain. The impaired ability of IL-4-/- mice in the late stage of T. gondii infection to produce IFN-gamma most likely contributes to their susceptibility for development of severe TE.
干扰素-γ对于预防弓形虫性脑炎（TE）的发展至关重要。由于白细胞介素-4（IL-4）可下调干扰素-γ的产生，我们研究了其在IL-4靶向突变（IL-4-/-）小鼠TE发病机制中的作用。IL-4-/-小鼠在经口感染刚地弓形虫ME49株包囊后6至20周内全部死亡；对照小鼠存活。感染后4周和8周，IL-4-/-小鼠脑中的弓形虫包囊和急性炎症灶数量显著多于对照小鼠，且速殖子特异性mRNA（通过逆转录聚合酶链反应检测）的量也更多。IL-4-/-小鼠血清中的弓形虫IgG2b和IgG3抗体水平略高于对照小鼠，但差异显著，而这些小鼠之间的IgM和IgG2a水平并无差异。两种品系小鼠的血清中均未检测到弓形虫IgG1和IgE抗体。通过逆转录聚合酶链反应检测到的干扰素-γ、肿瘤坏死因子-α、白细胞介素-6和白细胞介素-10 mRNA的量在感染的IL-4-/-小鼠和对照小鼠的脑中并无差异，尽管前者小鼠的脑中有更多的炎性单核细胞浸润。仅在感染的对照小鼠脑中检测到IL-4 mRNA。感染后8周，对照小鼠的脾细胞在体外用可溶性弓形虫抗原刺激后产生的干扰素-γ量显著多于IL-4-/-小鼠的脾细胞。这些结果表明，IL-4通过防止弓形虫包囊的形成和速殖子在脑中的增殖，对TE的发展具有保护作用。IL-4-/-小鼠在弓形虫感染后期产生干扰素-γ的能力受损，很可能是其易发生严重TE的原因。
