MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria:: No role for either in macrophage listericidal activity
MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria:: No role for either in macrophage listericidal activity
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DOI：
10.4049/jimmunol.169.7.3869
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发表时间：
2002-10-01
影响因子：
4.4
通讯作者：
Unanue, ER
中科院分区：
文献类型：
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作者：
Edelson, BT;Unanue, ER
我们评估了早期感染单核细胞增多性李斯特菌时体内对Toll样受体(TLR)信号的需求。缺乏TLR2的小鼠表现出与野生型小鼠相同的李斯特菌抵抗力。TLR2是识别革兰氏阳性肽聚糖所需的一种受体。然而，缺乏MyD88的小鼠在感染后第3天表现出严重的易感性，3-4个对数的李斯特菌负担更重，脾和肝脏病理严重。MyD88是所有TLR所使用的接头分子。尽管有证据表明巨噬细胞激活和MHC II类分子上调，但感染李斯特菌的MyD88缺陷小鼠也表现出显著的干扰素-γ、肿瘤坏死因子-α和NO反应减弱。我们证明，虽然对活体李斯特菌确实发生了轻微的MyD88非依赖性反应，但这些反应不足以进行正常的宿主防御。最后，我们进行了TLR2或MyD88缺陷的巨噬细胞直接感染李斯特氏菌的体外实验。尽管巨噬细胞NO和细胞因子的产生需要TLR信号来响应李斯特菌，但激活的巨噬细胞处理和直接杀死李斯特菌是通过TLR2和MyD88不依赖的机制实现的。
We have assessed the requirements for Toll-like receptor (TLR) signaling in vivo during early infection with Listeria monocytogenes. Mice deficient for TLR2, a receptor required for the recognition of Gram-positive peptidoglycan, showed equivalent Listeria resistance to wild-type mice. However, mice deficient for MyD88, an adaptor molecule used by all TLRs, showed profound susceptibility with 3-4 logs greater Listeria burden and severe spleen and liver pathology at day 3 postinfection. Listeria-infected MyD88-deficient mice also showed markedly diminished IFN-gamma, TNF-alpha, and NO responses, despite evidence of macrophage activation and up-regulation of MHC class II molecules. We demonstrate that although minor MyD88-independent responses to live Listeria do occur, these are insufficient for normal host defense. Lastly, we performed experiments in vitro in which macrophages deficient in TLR2 or MyD88 were directly infected with Listeria. Although TLR signaling was required for macrophage NO and cytokine production in response to Listeria, handling and direct killing of Listeria by activated macrophages occurred by TLR2- and MyD88-independent mechanisms.