Lüder C G, Lang T, Beuerle B, Gross U
Institute of Hygiene and Microbiology, University of Würzburg, Germany.
Clin Exp Immunol. 1998 May;112(2):308-16. doi: 10.1046/j.1365-2249.1998.00594.x.
Toxoplasma gondii is able to invade phagocytic cells of the monocyte-macrophage lineage and replicates within a parasitophorous vacuole. Since macrophages may activate specific T lymphocytes by presenting pathogen-derived antigens in association with molecules of the MHC, we investigated the in vitro expression of host cell molecules involved in antigen processing and presentation before and during infection of murine bone marrow-derived macrophages (BMM) with T. gondii. Fifty-one hours after addition of T. gondii tachyzoites at different parasite-to-host ratios, up-regulation of total MHC class II molecules by interferon-gamma (IFN-gamma) was dose-dependently abrogated in up to 50% of macrophages compared with uninfected control cultures. Quantitative analyses by flow cytometry revealed that the IFN-gamma-induced surface expression of class II antigens as well as the IFN-gamma-induced upregulation of class I molecules was significantly decreased in T. gondii-infected macrophage cultures compared with uninfected controls. However, the constitutive expression of MHC class I antigens was not altered after parasitic infection, and infected BMM remained clearly positive for these molecules. After infection of macrophages preactivated with IFN-gamma for 48 h, T. gondii also actively down-regulated an already established expression of MHC class II molecules. Furthermore, kinetic analysis revealed that the reduction in intracellular and plasma membrane-bound class II molecules started approximately 20 h after infection. While MHC class II antigens were most prominently reduced in parasite-positive host cells, culture supernatant from T. gondii-infected BMM cultures also significantly inhibited expression of these molecules in uninfected macrophages. However, down-regulation of MHC class II molecules was not mediated by an increased production of prostaglandin E2, IL-10, transforming growth factor-beta or nitric oxide by infected BMM compared with uninfected controls. Our data indicate that intracellular T. gondii interferes with the MHC class I and class II antigen presentation pathway of murine macrophages and this may be an important strategy for evasion from the host's immune response and for intracellular survival of the parasite.
刚地弓形虫能够侵入单核细胞-巨噬细胞系的吞噬细胞，并在寄生泡内进行复制。由于巨噬细胞可通过将病原体衍生的抗原与MHC分子结合来激活特定的T淋巴细胞，因此我们研究了在刚地弓形虫感染小鼠骨髓来源的巨噬细胞（BMM）之前和感染期间，参与抗原加工和呈递的宿主细胞分子的体外表达情况。以不同的寄生虫与宿主比例加入刚地弓形虫速殖子51小时后，与未感染的对照培养物相比，高达50%的巨噬细胞中干扰素-γ（IFN-γ）对总MHC II类分子的上调呈剂量依赖性减弱。流式细胞术的定量分析显示，与未感染的对照相比，刚地弓形虫感染的巨噬细胞培养物中IFN-γ诱导的II类抗原表面表达以及IFN-γ诱导的I类分子上调均显著降低。然而，寄生感染后MHC I类抗原的组成性表达未改变，且感染的BMM对这些分子仍呈明显阳性。在用IFN-γ预激活48小时的巨噬细胞感染后，刚地弓形虫也会积极下调已经建立的MHC II类分子表达。此外，动力学分析显示，细胞内和细胞膜结合的II类分子的减少在感染后约20小时开始。虽然在寄生虫阳性的宿主细胞中MHC II类抗原减少最为显著，但刚地弓形虫感染的BMM培养物的培养上清液也显著抑制未感染巨噬细胞中这些分子的表达。然而，与未感染的对照相比，感染的BMM产生的前列腺素E2、IL-10、转化生长因子-β或一氧化氮增加，并非MHC II类分子下调的介导因素。我们的数据表明，细胞内的刚地弓形虫会干扰小鼠巨噬细胞的MHC I类和II类抗原呈递途径，这可能是寄生虫逃避宿主免疫反应和在细胞内存活的重要策略。
