Mun Hye-Seong, Aosai Fumie, Norose Kazumi, Chen Mei, Piao Lian-Xun, Takeuchi Osamu, Akira Shizuo, Ishikura Hiroshi, Yano Akihiko
Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Int Immunol. 2003 Sep;15(9):1081-7. doi: 10.1093/intimm/dxg108.
To investigate the role of the Toll-like receptor (TLR) family in host defense against Toxoplasma gondii, we infected TLR2-, TLR4- and MyD88-deficient mice with the avirulent cyst-forming Fukaya strain of T. gondii. All TLR2- and MyD88-deficient mice died within 8 days, whereas all TLR4-deficient and wild-type mice survived after i.p. infection with a high dose of T. gondii. Peritoneal macrophages from T. gondii-infected TLR2- and MyD88-deficient mice did not produce any detectable levels of NO. T. gondii loads in the brain tissues of TLR2- and MyD88-deficient mice were higher than in those of TLR4-deficient and wild-type mice. Furthermore, high levels of IFN-gamma and IL-12 were produced in peritoneal exudate cells (PEC) of TLR4-deficient and wild-type mice after infection, but low levels of cytokines were produced in PEC of TLR2- and MyD88-deficient mice. On the other hand, high levels of IL-4 and IL-10 were produced in PEC of TLR2- and MyD88-deficient mice after infection, but low levels of cytokines were produced in PEC of TLR4-deficient and wild-type mice. The most remarkable histological changes with infiltration of inflammatory cells were observed in lungs of TLR2-deficient mice infected with T. gondii, where severe interstitial pneumonia occurred and abundant T. gondii were found.
为了研究Toll样受体（TLR）家族在宿主抵御刚地弓形虫中的作用，我们用无毒的形成包囊的刚地弓形虫深谷株感染了TLR2、TLR4和MyD88缺陷型小鼠。所有TLR2和MyD88缺陷型小鼠在8天内死亡，而所有TLR4缺陷型和野生型小鼠经腹腔注射高剂量刚地弓形虫感染后存活。来自刚地弓形虫感染的TLR2和MyD88缺陷型小鼠的腹腔巨噬细胞未产生任何可检测水平的一氧化氮。TLR2和MyD88缺陷型小鼠脑组织中的刚地弓形虫载量高于TLR4缺陷型和野生型小鼠。此外，感染后TLR4缺陷型和野生型小鼠的腹腔渗出细胞（PEC）中产生高水平的干扰素-γ和白细胞介素-12，但TLR2和MyD88缺陷型小鼠的PEC中产生的细胞因子水平较低。另一方面，感染后TLR2和MyD88缺陷型小鼠的PEC中产生高水平的白细胞介素-4和白细胞介素-10，但TLR4缺陷型和野生型小鼠的PEC中产生的细胞因子水平较低。在感染刚地弓形虫的TLR2缺陷型小鼠的肺部观察到最显著的组织学变化，伴有炎性细胞浸润，发生了严重的间质性肺炎，且发现大量刚地弓形虫。
