The role of toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCs) - Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2
The role of toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCs) - Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2
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DOI：
10.1074/jbc.m011615200
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发表时间：
2001-07-13
影响因子：
4.8
通讯作者：
Schumann, RR
中科院分区：
文献类型：
--
作者：
Michelsen, KS;Aicher, A;Schumann, RR
toll样受体（TLRs）是宿主免疫系统识别病原体的关键因素。树突状细胞（DC）在先天免疫反应和获得性免疫的启动中都是至关重要的，在这里，我们关注TLR配体相互作用在树突状细胞成熟中的潜在参与。研究了TLR2敲除小鼠和携带TLR4突变（C3H/HeJ）的小鼠在肽聚糖（PGN）、脂多糖（LPS）或脂质胆酸（LTAs）诱导下的DC成熟，所有刺激均诱导小鼠骨髓源性DC成熟。TLR2（-/-）小鼠在PGN刺激下缺乏成熟，通过主要组织相容性复合体II类的表达、CD86、细胞因子和趋化因子的产生、异硫氰酸荧光素-葡聚糖摄取和混合淋巴细胞反应来评估，同时对LPS完全响应。在LPS刺激下，C3H/HeJ小鼠也观察到类似的成熟缺失，来自两种不同类型细菌的LTAs诱导的DC成熟在TLR2（-/-）中严重受损，而C3H/HeJ小鼠对LTAs的反应方式与野生型小鼠相似。我们证明革兰氏阳性微生物（如PGN和LTA）刺激诱导DC成熟的效率与LPS相似。我们提供的证据表明，TLR2和TLR4与适当配体的相互作用对于细菌诱导的dc成熟至关重要。
Toll-like receptors (TLRs) have been found to be key elements in pathogen recognition by the host immune system. Dendritic cells (DCs) are crucial for both innate immune responses and initiation of acquired immunity, Here we focus on the potential involvement of TLR ligand interaction in DC maturation. TLR2 knockout mice and mice carrying a TLR4 mutation (C3H/HeJ) were investigated for DC maturation induced by peptidoglycan (PGN), lipopolysaccharide (LPS), or lipoteichoic acids (LTAs), All stimuli induced maturation of murine bone marrow-derived DCs in control mice. TLR2(-/-) mice lacked maturation upon stimulation with PGN, as assessed by expression of major histocompatibility complex class II, CD86, cytokine, and chemokine production, fluorescein isothiocyanate-dextran uptake, and mixed lymphocyte reactions, while being completely responsive to LPS. A similar lack of maturation was observed in C3H/HeJ mice upon stimulation with LPS, DC maturation induced by LTAs from two different types of bacteria was severely impaired in TLR2(-/-), whereas C3H/HeJ mice responded to LTAs in a manner similar to wild-type mice, We demonstrate that DC maturation is induced by stimuli from Gram-positive microorganisms, such as PGN and LTA, with similar efficiency as by LPS, Finally, we provide evidence that TLR2 and TLR4 interaction with the appropriate ligand is essential for bacteria-induced maturation of DCs.