Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Immunol Cell Biol. 2010 Nov-Dec;88(8):825-33. doi: 10.1038/icb.2010.52. Epub 2010 Apr 20.
Neospora caninum is an apicomplexan parasite responsible for major economic losses due to abortions in cattle. Toll-like receptors (TLRs) sense specific microbial products and direct downstream signaling pathways in immune cells, linking innate, and adaptive immunity. Here, we analyze the role of TLR2 on innate and adaptive immune responses during N. caninum infection. Inflammatory peritoneal macrophages and bone marrow-derived dendritic cells exposed to N. caninum-soluble antigens presented an upregulated expression of TLR2. Increased receptor expression was correlated to TLR2/MyD88-dependent antigen-presenting cell maturation and pro-inflammatory cytokine production after stimulation by antigens. Impaired innate responses observed after infection of mice genetically deficient for TLR2((-/-)) was followed by downregulation of adaptive T helper 1 (Th1) immunity, represented by diminished parasite-specific CD4(+) and CD8(+) T-cell proliferation, IFN-γ:interleukin (IL)-10 ratio, and IgG subclass synthesis. In parallel, TLR2(-/-) mice presented higher parasite burden than wild-type (WT) mice at acute and chronic stages of infection. These results show that initial recognition of N. caninum by TLR2 participates in the generation of effector immune responses against N. caninum and imply that the receptor may be a target for future prophylactic strategies against neosporosis.
刚地弓形虫是一种顶复门原虫寄生虫，可导致牛流产，给畜牧业造成重大经济损失。Toll 样受体 (TLR) 可识别特定的微生物产物，并在免疫细胞中直接引导下游信号通路，将先天免疫和适应性免疫联系起来。在这里，我们分析了 TLR2 在刚地弓形虫感染过程中对先天和适应性免疫反应的作用。暴露于刚地弓形虫可溶性抗原的炎症性腹膜巨噬细胞和骨髓来源的树突状细胞呈现 TLR2 的表达上调。受体表达增加与 TLR2/MyD88 依赖性抗原呈递细胞成熟和刺激后促炎细胞因子产生相关。在 TLR2((-/-)) 基因缺失的感染小鼠中观察到先天反应受损后，适应性 T 辅助 1 (Th1) 免疫受到抑制，表现为寄生虫特异性 CD4(+)和 CD8(+) T 细胞增殖、IFN-γ:白细胞介素 (IL)-10 比值和 IgG 亚类合成减少。同时，TLR2(-/-) 小鼠在急性和慢性感染阶段的寄生虫负荷均高于野生型 (WT) 小鼠。这些结果表明，TLR2 对刚地弓形虫的初始识别参与了针对刚地弓形虫的效应免疫反应的产生，并暗示该受体可能是未来抗新孢子虫病预防策略的一个靶点。
