Kudo Masamichi, Aosai Fumie, Mun Hye-Seong, Norose Kazumi, Akira Shizuo, Iwakura Yoichiro, Yano Akihiko
Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, 1-801 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Microbiol Immunol. 2004;48(8):617-28. doi: 10.1111/j.1348-0421.2004.tb03559.x.
The pathologic links between Toxoplasma gondii infections and renal diseases have not yet been established. Gamma interferon (IFN-gamma) and Toll-like receptors (TLRs) are involved in the host defense mechanism against T. gondii infection. The role of IFN-gamma and TLRs in renal function of T. gondii -infected mice was studied using wild type (WT), TLR2-deficient and TLR4-deficient mice perorally infected with cysts of an avirulent cyst-forming Fukaya strain of T. gondii. T. gondii was abundant in kidneys in IFN-gamma KO (GKO) mice as determined by a quantitative competitive-polymerase chain reaction (QC-PCR). But, T. gondii was not detected in kidneys in WT, TLR2-deficient and TLR4-deficient mice. Interestingly, renal function of TLR2-deficient and TLR4-deficient mice was damaged as evaluated by serum creatinine, serum blood urea nitrogen (BUN), and urine albumin/creatinine ratio (ACR), whereas renal function of GKO and WT mice was not damaged. Histopathology of TLR2-deficient mice exhibited glomerular and extracellular matrix swelling with advancing glomerular tissue proliferation, thickened Bowman's capsules and vacuolization of tubules. Renal immunofluorescence study of T. gondii -infected TLR2-deficient mice displayed positive staining of the glomerular basement membrane, mesangial areas and peritubular capillaries. The damage of kidney from TLR4-deficient mice was less severe compared to TLR2-deficient mice, and histopathological damage of kidney was not observed in WT and GKO mice. These results indicate that TLR2, but not IFN-gamma, plays a role in the protection of the renal function against T. gondii infection.
弓形虫感染与肾脏疾病之间的病理联系尚未确立。γ干扰素（IFN-γ）和Toll样受体（TLR）参与宿主抵抗弓形虫感染的防御机制。使用野生型（WT）、TLR2缺陷型和TLR4缺陷型小鼠，经口感染无毒力的福谷株弓形虫包囊，研究IFN-γ和TLR在弓形虫感染小鼠肾功能中的作用。通过定量竞争聚合酶链反应（QC-PCR）测定，IFN-γ基因敲除（GKO）小鼠的肾脏中弓形虫大量存在。但是，在WT、TLR2缺陷型和TLR4缺陷型小鼠的肾脏中未检测到弓形虫。有趣的是，通过血清肌酐、血清尿素氮（BUN）和尿白蛋白/肌酐比值（ACR）评估，TLR2缺陷型和TLR4缺陷型小鼠的肾功能受损，而GKO和WT小鼠的肾功能未受损。TLR2缺陷型小鼠的组织病理学表现为肾小球和细胞外基质肿胀，伴有肾小球组织增生、鲍曼囊增厚和肾小管空泡化。弓形虫感染的TLR2缺陷型小鼠的肾脏免疫荧光研究显示肾小球基底膜、系膜区和肾小管周围毛细血管呈阳性染色。与TLR2缺陷型小鼠相比，TLR4缺陷型小鼠的肾脏损伤较轻，WT和GKO小鼠未观察到肾脏组织病理学损伤。这些结果表明，TLR2而非IFN-γ在保护肾功能免受弓形虫感染中起作用。
