Toll-like Receptors and Cancer

先天免疫是机体抗细菌、抗病毒和抗肿瘤等的第一防线.Toll样受体(Toll-like recep-tors)是先天免疫的关键受体.它可以识别致病微生物的分子模式(pathogen associated moleculal pat-terns)而激活先天免疫细胞和进一步调整后天免疫系统.近来发现的Toll样受体在癌症的发生和发展中也扮演着重要角色.Toll样受体的激活因子在抗癌免疫疗法中可用作免疫调节剂(immunoadju-vants)或细胞毒素的药物.在这里,我们将简述当前关于Toll样受体的研究进展和在癌症的发生发展和癌症免疫疗法的作用.     

病毒固有免疫识别受体研究进展

固有免疫应答是机体抵御病毒入侵的第一道防线,其前提则是病毒固有免疫识别受体对病毒感染相关模式分子的识别.目前病毒固有免疫识别受体主要是Toll样受体家族和RIG样受体家族的成员.现就这些受体的特征及其在识别病毒感染相关模式分子过程中的作用作一综述.     

Toll样受体在卵巢癌中作用的研究进展

卵巢恶性肿瘤是病死率最高的妇科疾病,严重威胁女性的健康.固有性免疫系统发挥重要免疫防御作用,作用的关键是对病原体的识别,这一识别主要是通过Toll样受体(TLRs)完成的.TLRs是近年免疫学研究的焦点,其不仅通过对病原微生物的病原相关分子模式的识别激活固有性免疫应答,还引起细胞因子的释放,上调共刺激分子的表达,为适应性免疫的启动提供必要的活化信号.因此,TLRs在很多疾病的发生和进展中起重要作用.阐明TLRs和固有免疫在卵巢恶性肿瘤中的作用可能会为研究者提供一个更好地了解这种疾病的分子机制.此外,利用TLRs的激动剂或拮抗剂有希望成为对抗卵巢恶性肿瘤的新的免疫治疗方法.     

Toll样受体4与动脉粥样硬化关系的研究进展

动脉粥样硬化是心脑血管疾病的病理基础。但目前关于动脉粥样硬化的发病机制还不是很清楚。普遍认为免疫应答,包括固有免疫和适应性免疫在动脉粥样硬化的发生发展中起了重要作用。Toll受体4（TLR4）是抗原相关分子模式（PAMP）受体,在识别微生物感染、激发先天性免疫反应中发挥了重要作用。近来发现炎症在动脉粥样硬化发展的各个阶段均发挥了重要作用,虽然目前确切的证据还缺乏,但是越来越多的调查发现,病原体感染引起的分子和细胞的改变表明炎症具有这种作用。     

Toll样受体与肿瘤免疫

toll样受体（toll-like receptors,TLRs）是新近十余年发现的主要在哺乳动物细胞表面进化上高度保守的受体分子家族,主要通过识别病原相关分子模式（pathogen-associated molecular patterns,PAMPs）来迅速激活天然免疫系统,并且还能够诱导获得性免疫的产生。迄今为止,已经发现哺乳动物至少有13种toll样受体,其中人的toll样受体鉴定出11种（TLR1-TLR11）。在某些肿瘤中TLRs的表达发生量的变化,并且许多微生物组分和药物能够通过TLRs信号通路介导肿瘤的免疫治疗。     

Toll样受体的信号转导及抗感染免疫研究进展

Toll样受体(Toll-like receptors,TLRs)是进化中比较保守的一个受体家族,至少包括13个成员,Toll样受体能特异识别病原相关分子模式(PAMP),在天然免疫和获得性免疫中都发挥着重要的作用,是连接天然免疫和获得性免疫的桥梁。近年来,对TLRs信号转导的研究,特别是对TLRs负反馈的研究,进展非常迅速,它们在抗感染中起着重要的作用,特别是负反馈机制对信号的平衡调节在抗感染免疫中有重要作用。     

Toll样受体与抗感染免疫

随着Toll样受体 (TLRs)的发现 ,天然免疫在免疫应答中的重要性重新受到关注。TLRs如同天然免疫的“眼睛” ,监视与识别各种不同的病原相关分子模式 (pathogenassociatedmolecularpatterns,PAMPs) ,作为联系天然免疫与特异性免疫系统的桥梁 ,在识别和抵御各种病原微生物及其产物中发挥重要作用 ,本文对几种在抗感染免疫过程中起主要作用的TLRs作一综述     

Toll样受体与免疫排斥

随着Toll样受体(TLR)的发现,固有免疫应答如何调控适应性免疫应答已成为研究的热点。许多研究结果表明,微生物分子触发的病原体相关分子模式(PAMP)和TLR可以被内源性配体激活,并在哺乳动物体内表达。这些“危险信号”在器官移植后对于缺血再灌注损伤的发生、移植器官功能的影响及存活时间都起着重要的作用。     

中药对感染、自身免疫性疾病中Toll样受体表达影响的实验研究进展

近年来研究发现,在感染性疾病与自身免疫病中,Toll样受体的表达水平与疾病的发生、发展、转归及预后有关,因为传统中医药在该类疾病治疗中发挥了重要作用,使传统中药方剂对Toll样受体表达影响的研究尤为引人瞩目。本文就中药对感染与自身免疫性疾病中Toll样受体表达影响的实验研究做一简要综述。     

Toll样受体在寄生虫感染过程中的作用

Toll样受体（TLR）是天然免疫系统识别病原微生物的主要受体,在天然免疫反应中具有重要的作用。TLR通过识别病原相关模式分子以激活抗感染的天然免疫应答和适应性免疫应答。TLR信号通路可通过诱导炎性因子的产生在适应性免疫应答中发挥重要作用。本文就TLR在寄生虫感染中发挥的作用作一综述。     

Toll-like receptor stimulation in cancer: A pro- and anti-tumor double-edged sword

Toll-like receptors (TLRs) are a family of transmembrane receptors that recognize various pathogen- and damage-associated molecular pattern molecules playing an important role in inflammation by activating NF-кB. TLRs, mainly expressed by innate immune cells, are involved in inducing and regulating adaptive immune responses. However, the expression of TLRs has also been observed in many tumors, and their stimulation results in tumor progression or regression, depending on the TLR and tumor type. Here we review the role of TLRs in conferring anti- or pro-tumoral effects. The anti-tumoral effects can result from direct induction of tumor cell death and/or activation of efficient anti-tumoral immune responses, and the pro-tumoral effects may be due to inducing tumor cell survival and proliferation or by acting on suppressive or inflammatory immune cells in the tumor microenvironment.     

Toll样受体7作为新靶点在过敏性及自身免疫性疾病中的研究进展

Toll样受体(Toll-like receptors,TLRs)属于模式识别受体(pattern recognition receptors,PRRs)家族,通过迅速识别入侵微生物病原相关分子模式(pathogen-associated molecular patterns,PAMP)激活下游信号传导途径,引发机体的免疫反应,是连接固有免疫与适应性免疫的桥梁.目前在人类发现10种不同TLRs,分别命名为TLR1 ～TLR10.近年的研究显示,TLR7与过敏性疾病、自身免疫性疾病—过敏性哮喘、系统性红斑狼疮(systemic lupus erythematosus,SLE)等有密切的联系.TLR7的激活状态影响上述疾病的发生、发展和预后.这些证据预示TLR7可能作为潜在靶点为哮喘和SLE的治疗提供新的方向.     

肿瘤细胞表面TLR在促肿瘤发展中的作用和机制

自Toll样受体(Toll-like receptors,TLRs)发现以来,大量的研究主要集中于TLRs在天然免疫反应和调节适应性免疫中发挥的作用和机制。然而,近年来发现,除了表达于免疫系统的各种细胞外,TLRs还表达于肿瘤细胞表面,于是人们对肿瘤细胞TLRs在促进肿瘤发展中的作用和机制进行了探讨,发现TLRs能通过免疫逃避,以及促进肿瘤细胞存活、增殖和迁移等机制促进肿瘤发生和发展。因此,本文就肿瘤细胞上TLR在促进肿瘤中所发挥的作用及其机制进行综述。     

Redundant and regulatory roles for Toll‐like receptors in Leishmania infection

Toll‐like receptors (TLRs) are germline‐encoded, non‐clonal innate immune receptors, which are often the first receptors to recognize the molecular patterns on pathogens. Therefore, the immune response initiated by TLRs has far‐reaching consequences on the outcome of an infection. As soon as the cell surface TLRs and other receptors recognize a pathogen, the pathogen is phagocytosed. Inclusion of TLRs in the phagosome results in quicker phagosomal maturation and stronger adaptive immune response, as TLRs influence co‐stimulatory molecule expression and determinant selection by major histocompatibility complex (MHC) class II and MHC class I for cross‐presentation. The signals delivered by the TCR–peptide–MHC complex and co‐stimulatory molecules are indispensable for optimal T cell activation. In addition, the cytokines induced by TLRs can skew the differentiation of activated T cells to different effector T cell subsets. However, the potential of TLRs to influence adaptive immune response into different patterns is severely restricted by multiple factors: gross specificity for the molecular patterns, lack of receptor rearrangements, sharing of limited number of adaptors that assemble signalling complexes and redundancy in ligand recognition. These features of apparent redundancy and regulation in the functioning of TLRs characterize them as important and probable contributory factors in the resistance or susceptibility to an infection.     

Direct and indirect role of Toll-like receptors in T cell mediated immunity

Toll-like receptors (TLR) are pathogen-associated molecular patterns (PAMPs) recognition receptors that playan important role in protective immunity against infection and inflammation.They act as central integrators ofa wide variety of signals,responding to diverse agonists of microbial products.Stimulation of Toll-like receptorsby microbial products leads to signaling pathways that activate not only innate,but also adaptive immunity byAPC dependent or independent mechanisms.Recent evidence revealed that TLR signals played a determiningrole in the skewing of na(?)ve T cells towards either Th1 or Th2 responses.Activation of Toll-like receptors alsodirectly or indirectly influences regulatory T cell functions.Therefore,TLRs are required in both immuneactivation and immune regulation.Study of TLRs has significantly enhanced our understanding of innate andadaptive immune responses and provides novel therapeutic approaches against infectious and inflammatorydiseases.Cellular & Molecular Immunology.2004;1(4):239-246.     

Toll-like receptors: critical proteins linking innate and acquired immunity

Recognition of pathogens is mediated by a set of germline-encoded receptors that are referred to as pattern-recognition receptors (PRRs). These receptors recognize conserved molecular patterns (pathogen-associated molecular patterns), which are shared by large groups of microorganisms. Toll-like receptors (TLRs) function as the PRRs in mammals and play an essential role in the recognition of microbial components. The TLRs may also recognize endogenous ligands induced during the inflammatory response. Similar cytoplasmic domains allow TLRs to use the same signaling molecules used by the interleukin 1 receptors (IL-1Rs): these include MyD88, IL-1R--associated protein kinase and tumor necrosis factor receptor--activated factor 6. However, evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.     

先天免疫的研究进展

近来,关于先天免疫的研究有了突飞猛进的进展。特别是在关于模式识别受体的发现和功能研究方面。模式识别受体能识别病原相关的分子模式。先天免疫不但提供抗感染的第一防线而且调控后天获得性免疫的激活。如果没有先天免疫,后天获得性免疫的功能会变得很微弱。Toll样受体是先天免疫的关键感受器和研究最多的模式识别受体。激活的Toll样受体信号传导通路可以很快引起与炎性反应和免疫反应相关的各种基因的表达。所有这些关于研究Toll样受体及其信号通路的新见解已经开始改变我们对炎性反应和免疫反应相关疾病的预防和治疗。