PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells
PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells
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中性粒细胞、经典单核细胞和树突状细胞上细胞表面 TLR5 的 PRAT4A 依赖性表达
DOI：
10.1093/intimm/dxs068
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Miyake K
中科院分区：
文献类型：
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作者：
Shibata T;Takemura N;Motoi Y;Goto Y;Karuppuchamy T;Izawa K;Li X;Akashi-Takamura S;Tanimura N;Kunisawa J;Kiyono H;Akira S;Kitamura T;Kitaura J;Uematsu S;Miyake K
摘要Toll样受体5(TLR5)是细菌鞭毛蛋白的感受器，可启动先天和获得性免疫反应，与感染性疾病、结肠炎和代谢综合征有关。尽管TLR5被认为属于细胞表面TLRs，但细胞表面的表达从未得到证实。此外，目前还不清楚哪些类型的免疫细胞表达TLR5并有助于鞭毛依赖的反应。本研究建立了抗小鼠TLR5的单抗，并对免疫细胞表面TLR5的表达进行了研究。巨噬细胞株J774在细胞表面表达内源性TLR5，并对鞭毛蛋白产生IL-6和G-CSF。通过沉默与TLR4A相关的TLR特异性伴侣蛋白(PRAT4A)，细胞表面TLR5的表达和鞭毛蛋白诱导的反应完全被取消，表明TLR5是PRAT4A的另一个客户。在活体免疫细胞中，TLR5细胞表面主要见于中性粒细胞和CD11bhiLY6典型单核细胞，见于骨髓、循环、脾和炎性病变。典型的单核细胞对鞭毛蛋白的反应产生细胞因子，而不是中性粒细胞。脾CD8、−、CD4+常规树突状细胞和CD11chiCD11bHilamina固有树突状细胞也表达细胞表面TLR5。总的来说，TLR5的细胞表面表达依赖于PRAT4A，并且仅限于中性粒细胞、经典单核细胞和特定的DC亚群。
AbstractToll-like receptor 5 (TLR5), a sensor for bacterial flagellin, mounts innate and adaptive immune responses, and has been implicated in infectious diseases, colitis and metabolic syndromes. Although TLR5 is believed to belong to cell surface TLRs, cell surface expression has never been verified. Moreover, it has remained unclear which types of immune cells express TLR5 and contribute to flagellin-dependent responses. In this study we established an anti-mouse TLR5 monoclonal antibody and studied the cell surface expression of TLR5 on immune cells. The macrophage cell line J774 expressed endogenous TLR5 on the cell surface and produced IL-6 and G-CSF in response to flagellin. Cell surface expression of TLR5 and flagellin-induced responses were completely abolished by silencing a TLR-specific chaperone protein associated with TLR4 A (PRAT4A), demonstrating that TLR5 is another client of PRAT4A. In thein vivoimmune cells, cell surface TLR5 was mainly found on neutrophils and CD11bhiLy6Chiclassical monocytes in the bone marrow, circulation, spleen and inflammatory lesions. Ly6Chiclassical monocytes, but not neutrophils, produced cytokines in response to flagellin. Splenic CD8−CD4+conventional dendritic cells and CD11chiCD11bhilamina propria DCs, also clearly expressed cell surface TLR5. Collectively, cell surface expression of TLR5 is dependent on PRAT4A and restricted to neutrophils, classical monocytes and specific DC subsets.