Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice
Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice
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DOI：
10.1128/iai.05680-11
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发表时间：
2012-04-01
影响因子：
3.1
通讯作者：
Aosai, Fumie
中科院分区：
文献类型：
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作者：
Washino, Takuya;Moroda, Masataka;Aosai, Fumie
白介素1受体拮抗剂(IL-1ra)缺陷的BALB/c小鼠出现类似人类类风湿性关节炎的自发性关节炎。我们在此报告，感染弓形虫，一种细胞内的原虫，能够改善IL-1ra缺乏小鼠的关节炎的自发发展。在弓形虫感染的小鼠中，关节炎的发生发展被推迟，关节炎的严重程度评分被显着抑制。经口感染后1周，肠系膜淋巴结(MLN)和脾CD11c(+)细胞IL-12p40mRNA的表达显著增加。虽然CD11c(+)细胞也产生IL-10、IL-1β和IL-6，但弓形虫感染小鼠的CD4(+)T细胞在MLN和脾中均表达高水平的T-bet和γ-干扰素(IFN-γ)mRNA。感染小鼠GATA-3/IL-4或ROR-γt/IL-17 mRNA表达水平降低，提示Th1细胞极化，Th2和Th17细胞极化减弱。关节炎的严重程度与Th1细胞极化和Th17细胞减少有关，表明弓形虫来源的Th1应答对IL-1ra缺陷小鼠Th17细胞介导的关节炎具有保护作用。
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-1 beta, and IL-6, CD4(+) T cells from T. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-gamma) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or ROR gamma t/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.