Toll样受体调节中性粒细胞免疫作用的研究进展

Toll样受体（TLR）是固有免疫系统中特异的I型跨膜受体及病原模式识别受体。TLR能特异地识别病原体相关分子模式（PAMP）,构成机体抵御病原微生物的第一道防线,因而在固有免疫系统中发挥重要作用,而且TLR还能调节适应性免疫,是连接固有免疫和适应性免疫的桥梁。中性粒细胞（PMN）是机体最重要的炎性细胞,在固有免疫中扮演着十分重要的角色,对炎症的发生、发展及转归起了关键的作用。作为重要受体的TLR能诱导PMN的生存与活化,在急性炎症反应、细胞信号转导和细胞凋亡中起着重要作用。     

中性粒细胞中Toll样受体的表达与功能

中性粒细胞是最重要的固有免疫细胞,通过黏附、趋化、识别、脱颗粒、杀伤和降解等一系列过程杀灭病原微生物,介导炎症反应。整个过程受到众多细胞因子及其受体的调控,Toll样受体(TLR)作为最主要的固有免疫识别受体,在中性粒细胞的聚集、活化和凋亡中都起着重要的调控作用。     

Toll样受体研究进展

Toll最早在果蝇中被发现。Toll受体蛋白 (d Toll)不仅参与果蝇胚胎发育时背腹的形成 ,而且参与成蝇对病原体侵袭的先天性免疫应答 ,是微生物诱导成年果蝇产生抗菌肽的信号转导通道的门户。 Toll样受体是先天性模式识别受体 ,在细胞活化信号的转导中起重要作用。它作为联系先天性与获得性免疫系统的桥梁 ,备受人们关注     

Toll样受体信号介导细胞凋亡的研究进展

细胞凋亡在病毒、细菌等感染的过程中和肿瘤等疾病的发生发展中起至关重要的作用。Toll样受体(TLR)存在于巨噬细胞、肿瘤细胞等细胞表面,能直接识别并结合病原微生物和宿主细胞表面的病原相关分子模式,然后通过髓样分化因子88/Fas相关死亡结构域/caspase-8、TIR结构域接头蛋白/蛋白激酶/干扰素调节因子和核因子κB路径等信号途径对巨噬细胞、肿瘤细胞等细胞的凋亡起调节作用。随着对TLR介导的细胞凋亡中Fas相关死亡结构域、TIR结构域接头蛋白等多种信号分子的深入研究,有助于了解它们在细胞凋亡中的作用,并为感染和肿瘤等疾病的分子靶向治疗提供新的目标。     

Toll样受体介导的先天性抗病毒免疫反应研究进展

TLRs是先天性免疫系统最重要的模式识别受体,通过识别病毒的PAMPs/DAMPs,活化依赖和非依赖于MyD88的信号通路,诱导I-IFN、炎性因子和趋化因子等的释放,发挥抗病毒作用.现就TLRs的基本概况、结构特征、抗病毒信号通路及对不同病毒的天然免疫反应等相关研究进展进行简要综述.     

肥大细胞Toll样受体的研究进展

肥大细胞是重要的效应和调节性免疫细胞,广泛分布于皮肤、淋巴组织、子宫、膀胱以及呼吸道和消化道黏膜和黏膜下毛细血管、淋巴管周围的结缔组织中.     

Toll样受体的研究进展

Toll样受体(Toll-like receptors,TLR)是近年来备受关注的一种病原体识别受体,它在固有免疫中通过对病原体相关的分子模式(pathogen-associated molecular patterns,PAMP)的识别发挥作用,通过刺激信号的级联反应导致细胞因子的产生和协同刺激因子的表达,在天然免疫和获得性免疫中起到了桥梁的作用。鉴于TLR在免疫学,分子生物学以及临床研究中的重要意义,自发现至今,众多相关的研究不断展开。本综述将回顾TLR发现以来主要的研究进展,探讨TLR的临床联系以及展望未来TLR可能的研究方向。     

Toll样受体与乙型病毒性肝炎的研究进展

Toll样受体在抗病原微生物感染和调节固有免疫和获得性免疫中起着重要的作用,是连接固有免疫与获得性免疫的重要桥梁。TLRs在乙型病毒性肝炎中的作用复杂,以其特异的模式识别方式和相互调节的网络反应参与慢性乙型肝炎、慢性重型肝炎的发病。     

Toll样受体与造血

Toll样受体（TLR）是近年来发现的一类天然免疫受体,在天然免疫及获得性免疫过程中均发挥非常重要的作用。对TLR的深入研究表明,TLRs在造血相关细胞（造血干／祖细胞、间充质干细胞、血管内皮细胞等）上均有不同程度的表达,并且发挥一定生物学效应。     

Toll样受体介导抗HBV感染免疫

Toll样受体(TLRs)的发现,使人们对HBV感染免疫有了新的认识.目前研究认为,TLRs除了介导抗HBV感染天然免疫外,还能促进树突状细胞(DC)成熟,调节Th1/Th2型免疫,参与抗HBV特异性免疫,同时,HBV也影响某些TLRs的表达,这可能是HBV感染慢性化的原因之一.进一步明确TLRs在HBV感染免疫中的作用,可为HBV感染的治疗提供一个新的切入点.     

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.     

Moderate exercise improves leucocyte function and decreases inflammation in diabetes

The genesis and progression of diabetes occur due in part to an uncontrolled inflammation profile with insulin resistance, increased serum levels of free fatty acids (FFA), proinflammatory cytokines and leucocyte dysfunction. In this study, an investigation was made of the effect of a 3‐week moderate exercise regimen on a treadmill (60% of VO_2max, 30 min/day, 6 days a week) on inflammatory markers and leucocyte functions in diabetic rats. The exercise decreased serum levels of tumour necrosis factor (TNF)‐α (6%), cytokine‐induced neutrophil chemotactic factor 2 alpha/beta (CINC‐2α/β) (9%), interleukin (IL)‐1β (34%), IL‐6 (86%), C‐reactive protein (CRP) (41%) and FFA (40%) in diabetic rats when compared with sedentary diabetic animals. Exercise also attenuated the increased responsiveness of leucocytes from diabetics when compared to controls, diminishing the reactive oxygen species (ROS) release by neutrophils (21%) and macrophages (28%). Exercise did not change neutrophil migration and the proportion of neutrophils and macrophages in necrosis (loss of plasma membrane integrity) and apoptosis (DNA fragmentation). Serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) were not modified in the conditions studied. Therefore, physical training did not alter the integrity of muscle cells. We conclude that moderate physical exercise has marked anti‐inflammatory effects on diabetic rats. This may be an efficient strategy to protect diabetics against microorganism infection, insulin resistance and vascular complications.     

Neutrophils in the periodontium: Interactions with pathogens and roles in tissue homeostasis and inflammation

Neutrophils are of key importance in periodontal health and disease. In their absence or when they are functionally defective, as occurs in certain congenital disorders, affected individuals develop severe forms of periodontitis in early age. These observations imply that the presence of immune-competent neutrophils is essential to homeostasis. However, the presence of supernumerary or hyper-responsive neutrophils, either because of systemic priming or innate immune training, leads to imbalanced host–microbe interactions in the periodontium that culminate in dysbiosis and inflammatory tissue breakdown. These disease-provoking imbalanced interactions are further exacerbated by periodontal pathogens capable of subverting neutrophil responses to their microbial community's benefit and the host's detriment. This review attempts a synthesis of these findings for an integrated view of the neutrophils' ambivalent role in periodontal disease and, moreover, discusses how some of these concepts underpin the development of novel therapeutic approaches to treat periodontal disease.     

Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo

Background Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. Objective To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. Methods After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. Results Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. Conclusions The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The disttibution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.     

Priming of the neutrophil respiratory burst: role in host defense and inflammation

Neutrophils are the major circulating white blood cells in humans. They play an essential role in host defense against pathogens. In healthy individuals, circulating neutrophils are in a dormant state with very low efficiency of capture and arrest on the quiescent endothelium. Upon infection and subsequent release of pro-inflammatory mediators, the vascular endothelium signals to circulating neutrophils to roll, adhere, and cross the endothelial barrier. Neutrophils migrate toward the infection site along a gradient of chemo-attractants, then recognize and engulf the pathogen. To kill this pathogen entrapped inside the vacuole, neutrophils produce and release high quantities of antibacterial peptides, proteases, and reactive oxygen species (ROS). The robust ROS production is also called ‘the respiratory burst’, and the NADPH oxidase or NOX2 is the enzyme responsible for the production of superoxide anion, leading to other ROS. In vitro, several soluble and particulate agonists induce neutrophil ROS production. This process can be enhanced by prior neutrophil treatment with ‘priming’ agents, which alone do not induce a respiratory burst. In this review, we will describe the priming process and discuss the beneficial role of controlled neutrophil priming in host defense and the detrimental effect of excessive neutrophil priming in inflammatory diseases.     

Neutrophil recognition of bacterial DNA and Toll-like receptor 9-dependent and -independent regulation of neutrophil function

Neutrophils are essential for host defense and detect the presence of invading microorganisms through recognition of pathogen-associated molecular patterns. Among these receptors are Toll-like receptors (TLRs). Neutrophils express all known TLRs except for TLR3. TLR9, localized intracellularly, is to date the best characterized sensor for bacterial DNA, containing short sequences of unmethylated CpG motifs, though TLR9-independent intracellular DNA recognition mechanism(s) may also exist. Bacterial DNA has profound impact on neutrophil functions; it promotes neutrophil trafficking in vivo, induces chemokine expression, regulates expression of adhesion molecules, enhances phagocyte activity, and rescues neutrophils from constitutive apoptosis. TLR9 stimulation results in alterations in cellular redox balance, peroxynitrite formation, activation of the mitogen-activated protein kinase, PI3-kinase, and Jun N-terminal kinase pathways and/or nuclear factor κB and AP-1. These features identify an important role for bacterial DNA and TLR9 signaling in the regulation of neutrophil functions that are critical for optimal expression as well as for resolution of the inflammatory response.     

Possible mechanisms for the regulation of neutrophil apoptosis during allergic inflammation

The neutrophil-mediated inflammatory response is regulated via activation of the apoptosis program, which decreases the degree of tissue alteration. In rabbits with allergic inflammation a significant negative correlation was revealed between the intensity of neutrophil apoptosis and blood interferon-γ concentration. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 3, pp. 273–275, March, 2007     

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.