Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity.
Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity.
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DOI：
10.1172/jci14704
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发表时间：
2002-05
期刊：
影响因子：
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通讯作者：
V. Supajatura;H. Ushio;A. Nakao;S. Akira;K. Okumura;C. Ra;H. Ogawa
中科院分区：
文献类型：
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作者：
V. Supajatura;H. Ushio;A. Nakao;S. Akira;K. Okumura;C. Ra;H. Ogawa
Toll样受体2（TLR 2）和TLR 4在微生物攻击的早期先天免疫应答中起重要作用。为了阐明TLR 2和TLR 4在肥大细胞中的功能作用，我们检测了来自TLR 2或TLR 4基因靶向小鼠的骨髓源性肥大细胞（BMMC）。来自金黄色葡萄球菌的肽聚糖（PGN）以TLR 2依赖性方式刺激肥大细胞产生TNF-α、IL-4、IL-5、IL-6和IL-13，但不产生IL-1 β。相反，大肠杆菌的LPS以TLR 4依赖的方式刺激肥大细胞产生TNF-α、IL-1 β、IL-6和IL-13，但不产生IL-4和IL-5。此外，TLR 2-而不是TLR 4-依赖的肥大细胞刺激导致肥大细胞脱粒和Ca 2+动员。在急性脓毒症的肥大细胞依赖性模型中，小鼠骨髓基质细胞的TLR 4缺乏导致显著更高的死亡率，这是因为腹膜腔中有缺陷的中性粒细胞募集和促炎细胞因子的产生。皮内注射PGN通过TLR 2依赖性激活皮肤中的肥大细胞导致血管舒张和炎症增加。总之，这些结果表明，肥大细胞通过各自的微配体通过TLR 2或TLR 4的直接活化有助于先天性和过敏性免疫应答。
Toll-like receptor 2 (TLR2) and TLR4 play important roles in the early innate immune response to microbial challenge. To clarify the functional roles of TLRs 2 and 4 in mast cells, we examined bone marrow-derived mast cells (BMMCs) from TLR2 or TLR4 gene-targeted mice. Peptidoglycan (PGN) from Staphylococcus aureus stimulated mast cells in a TLR2-dependent manner to produce TNF-alpha, IL-4, IL-5, IL-6, and IL-13, but not IL-1beta. In contrast, LPS from Escherichia coli stimulated mast cells in a TLR4-dependent manner to produce TNF-alpha, IL-1beta, IL-6, and IL-13, but not IL-4 nor IL-5. Furthermore, TLR2- but not TLR4-dependent mast cell stimulation resulted in mast cell degranulation and Ca2+ mobilization. In a mast cell-dependent model of acute sepsis, TLR4 deficiency of BMMCs in mice resulted in significantly higher mortality because of defective neutrophil recruitment and production of proinflammatory cytokines in the peritoneal cavity. Intradermal injection of PGN led to increased vasodilatation and inflammation through TLR2-dependent activation of mast cells in the skin. Taken together, these results suggest that direct activation of mast cells via TLR2 or TLR4 by respective microligands contributes to innate and allergic immune responses.