Department of Infection and Host Defense, Chiba University Graduate School of Medicine, Chiba, Japan.
Infect Immun. 2012 Apr;80(4):1437-44. doi: 10.1128/IAI.05680-11. Epub 2012 Jan 30.
Interleukin 1 receptor antagonist (IL-1Ra)-deficient BALB/c mice develop spontaneous arthritis resembling human rheumatoid arthritis. We herein report that infection with Toxoplasma gondii, an intracellular protozoan, is capable of ameliorating the spontaneous development of arthritis in IL-1Ra-deficient mice. The onset of arthritis development was delayed and the severity score of arthritis was significantly suppressed in T. gondii-infected mice. Expression of IL-12p40 mRNA from CD11c(+) cells of mesenteric lymph nodes (mLN) and spleen markedly increased at 1 week after peroral infection. While CD11c(+) cells also produced IL-10, IL-1β, and IL-6, CD4(+) T cells from T. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-γ) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or RORγt/IL-17 mRNA decreased in the infected mice, indicating Th1 cell polarization and the reduction of Th2 and Th17 cell polarization. The severity of arthritis was related to Th1 cell polarization accompanied by Th17 cell reduction, demonstrating the protective role of the T. gondii-derived Th1 response against Th17 cell-mediated arthritis in IL-1Ra-deficient mice.
白细胞介素 1 受体拮抗剂（IL-1Ra）缺陷型 BALB/c 小鼠自发形成类似于人类类风湿关节炎的关节炎。我们在此报告，感染细胞内原生动物弓形虫能够改善 IL-1Ra 缺陷型小鼠自发关节炎的发展。关节炎发病的潜伏期延长，关节炎严重程度评分在弓形虫感染的小鼠中显著降低。经口感染后 1 周，肠系膜淋巴结（mLN）和脾中的 CD11c（+）细胞中 IL-12p40 mRNA 的表达明显增加。虽然 CD11c（+）细胞也产生 IL-10、IL-1β 和 IL-6，但来自弓形虫感染的小鼠的 CD4（+）T 细胞在 mLN 和脾中均表达显著高水平的 T-bet 和伽马干扰素（IFN-γ）mRNA。感染小鼠的 GATA-3/IL-4 mRNA 或 RORγt/IL-17 mRNA 水平降低，表明 Th1 细胞极化和 Th2 和 Th17 细胞极化减少。关节炎的严重程度与 Th1 细胞极化有关，同时 Th17 细胞减少，表明弓形虫衍生的 Th1 反应对 IL-1Ra 缺陷型小鼠中 Th17 细胞介导的关节炎具有保护作用。
