Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Expert Rev Mol Med. 2011 Oct 4;13:e31. doi: 10.1017/S1462399411002018.
Toxoplasma gondii is an obligate intracellular protozoan parasite that causes various diseases, including lymphadenitis, congenital infection of fetuses and life-threatening toxoplasmic encephalitis in immunocompromised individuals. Interferon-gamma (IFN-γ)-mediated immune responses are essential for controlling tachyzoite proliferation during both acute acquired infection and reactivation of infection in the brain. Both CD4+ and CD8+ T cells produce this cytokine in response to infection, although the latter has more potent protective activity. IFN-γ can activate microglia, astrocytes and macrophages, and these activated cells control the proliferation of tachyzoites using different molecules, depending on cell type and host species. IFN-γ also has a crucial role in the recruitment of T cells into the brain after infection by inducing expression of the adhesion molecule VCAM-1 on cerebrovascular endothelial cells, and chemokines such as CXCL9, CXCL10 and CCL5. A recent study showed that CD8+ T cells are able to remove T. gondii cysts, which represent the stage of the parasite in chronic infection, from the brain through their perforin-mediated activity. Thus, the resistance to cerebral infection with T. gondii requires a coordinated network using both IFN-γ- and perforin-mediated immune responses. Elucidating how these two protective mechanisms function and collaborate in the brain against T. gondii will be crucial in developing a new method to prevent and eradicate this parasitic infection.
刚地弓形虫是一种专性细胞内寄生的原虫，可引起各种疾病，包括淋巴结炎、胎儿先天性感染以及免疫功能低下个体的致命性弓形体脑炎。干扰素-γ（IFN-γ）介导的免疫反应对于控制急性获得性感染和大脑感染再激活期间速殖子的增殖至关重要。CD4+和 CD8+T 细胞均可响应感染产生这种细胞因子，尽管后者具有更强的保护活性。IFN-γ 可以激活小胶质细胞、星形胶质细胞和巨噬细胞，这些激活的细胞通过不同的分子控制速殖子的增殖，具体取决于细胞类型和宿主物种。IFN-γ 通过诱导脑血管内皮细胞表达粘附分子 VCAM-1，以及趋化因子如 CXCL9、CXCL10 和 CCL5，在感染后还在 T 细胞募集到大脑中发挥关键作用。最近的一项研究表明，CD8+T 细胞能够通过其穿孔素介导的活性从大脑中清除刚地弓形虫包囊，这是慢性感染阶段的寄生虫。因此，抵抗大脑感染刚地弓形虫需要使用 IFN-γ 和穿孔素介导的免疫反应协调网络。阐明这两种保护机制在大脑中如何对抗刚地弓形虫发挥作用并相互协作对于开发预防和消除这种寄生虫感染的新方法至关重要。
