Yarovinsky Felix, Zhang Dekai, Andersen John F, Bannenberg Gerard L, Serhan Charles N, Hayden Matthew S, Hieny Sara, Sutterwala Fayyaz S, Flavell Richard A, Ghosh Sankar, Sher Alan
Immunobiology Section, Laboratory of Parasitic Diseases; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Science. 2005 Jun 10;308(5728):1626-9. doi: 10.1126/science.1109893. Epub 2005 Apr 28.
Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, relatively little is known about their function in the innate response to eukaryotic microorganisms. Here we identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs through TLR11 and is the first chemically defined ligand for this TLR. Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens.
哺乳动物的Toll样受体（TLRs）在树突状细胞（DCs）对病原体的天然识别中发挥着重要作用。虽然TLRs显然参与了对细菌和病毒的检测，但对于它们在对真核微生物的天然免疫反应中的功能却知之甚少。在这里，我们从原生动物寄生虫刚地弓形虫中鉴定出一种肌动蛋白结合蛋白样分子，该分子在小鼠DCs中引发了强烈的白细胞介素-12（IL-12）反应，且该反应依赖于髓样分化因子88。刚地弓形虫肌动蛋白结合蛋白通过TLR11激活DCs，并且是该TLR的首个化学定义配体。此外，体内寄生虫诱导的IL-12产生和对感染的最佳抵抗力需要TLR11，从而确立了该受体在宿主对原生动物病原体识别中的作用。
