Yarovinsky Felix, Sher Alan
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bld. 50, Rm 6144, 50 South Drive MSC 8003, Bethesda, MD 20892-8003, USA.
Int J Parasitol. 2006 Mar;36(3):255-9. doi: 10.1016/j.ijpara.2005.12.003. Epub 2006 Jan 13.
Toxoplasma gondii potently stimulates IFN-gamma production by both the innate and adaptive immune system as part of its host adaptation. This response is known to be dependent on an Myeloid Differentiation factor 88 signaling pathway used by Toll-like receptors (TLRs), a family of proteins involved in the recognition of microbial molecular patterns. In the following review, we summarise the evidence for specific TLR function in host resistance to T. gondii focusing on the recent discovery in the parasite of a profilin-like ligand that potently stimulates TLR11 and regulates the production of IL-12, a cytokine necessary for the protective IFN-gamma response. In addition, we discuss the hypothesis that TLR11 may have evolved as a general pattern recognition receptor for apicomplexan protozoa and that as highly conserved proteins associated with actin-based motility, profilins are logical ligand targets for this form of pathogen detection. Finally, we review the evidence for involvement of other TLR and TLR ligands in host resistance to T. gondii and discuss how such receptors might synergise with TLR11 in the innate response to the parasite.
作为其宿主适应性的一部分,刚地弓形虫能强烈刺激先天性和适应性免疫系统产生γ干扰素。已知这种反应依赖于髓样分化因子88信号通路,该通路由Toll样受体(TLR)使用,TLR是一类参与识别微生物分子模式的蛋白质。在以下综述中,我们总结了特定TLR在宿主抗刚地弓形虫感染中的功能证据,重点关注最近在该寄生虫中发现的一种肌动蛋白结合蛋白样配体,它能强烈刺激TLR11并调节IL-12的产生,IL-12是保护性γ干扰素反应所必需的一种细胞因子。此外,我们讨论了这样一种假说,即TLR11可能已经进化成为一种针对顶复门原生动物的通用模式识别受体,并且作为与基于肌动蛋白的运动相关的高度保守蛋白质,肌动蛋白结合蛋白是这种病原体检测形式的合理配体靶点。最后,我们回顾了其他TLR及其配体参与宿主抗刚地弓形虫感染的证据,并讨论了这些受体如何在对该寄生虫的先天性反应中与TLR11协同作用。