Benson Alicia, Pifer Reed, Behrendt Cassie L, Hooper Lora V, Yarovinsky Felix
Department of Immunology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Cell Host Microbe. 2009 Aug 20;6(2):187-96. doi: 10.1016/j.chom.2009.06.005.
Toxoplasma gondii is a universally distributed pathogen that infects over one billion people worldwide. Host resistance to this protozoan parasite depends on a Th1 immune response with potent production of the cytokines interleukin-12 and interferon gamma. Although Toll-like receptor 11 (TLR11) plays a major role in controlling Th1 immunity to this pathogen in mice, this innate immune receptor is nonfunctional in humans, and the mechanisms of TLR11-independent sensing of T. gondii remain elusive. Here, we show that oral infection by T. gondii triggers a TLR11-independent but MyD88-dependent Th1 response that is impaired in TLR2xTLR4 double knockout and TLR9 single knockout mice. These mucosal innate and adaptive immune responses to T. gondii rely on the indirect stimulation of dendritic cells by normal gut microflora. Thus, our results reveal that gut commensal bacteria can serve as molecular adjuvants during parasitic infection, providing indirect immunostimulation that protects against T. gondii in the absence of TLR11.
刚地弓形虫是一种广泛分布的病原体，全球感染人数超过10亿。宿主对这种原生动物寄生虫的抵抗力取决于具有强大细胞因子白细胞介素-12和干扰素γ产生能力的Th1免疫反应。尽管Toll样受体11（TLR11）在小鼠中对该病原体的Th1免疫控制中起主要作用，但这种先天免疫受体在人类中无功能，且TLR11非依赖性感知刚地弓形虫的机制仍不清楚。在此，我们表明刚地弓形虫的口服感染引发了一种TLR11非依赖性但MyD88依赖性的Th1反应，这种反应在TLR2×TLR4双敲除和TLR9单敲除小鼠中受损。这些对刚地弓形虫的黏膜先天和适应性免疫反应依赖于正常肠道微生物群对树突状细胞的间接刺激。因此，我们的结果表明，肠道共生细菌在寄生虫感染期间可作为分子佐剂，在缺乏TLR11的情况下提供间接免疫刺激以抵御刚地弓形虫。
