哺乳动物Toll样受体对结核分枝杆菌的控制

针对胞内菌结核分枝杆菌最为有效的免疫应答主要取决于天然免疫应答对侵入细菌的早期发现及获得性免疫应答的活化。Toll样受体在天然免疫应答发现分枝杆菌相关性分子和介导抗菌效应分子的分泌上起作用。它能调节一些免疫调节分子,这些分子能促进基于Th1细胞的T细胞发育。因此,Toll样受体的活化在抗微生物感染的机制上起一定的作用。     

Toll样受体与肿瘤免疫

Toll样受体(Toll-like receptor)是天然免疫系统中最重要的模式识别受体,在病原体感染过程中对入侵病原体的识别,激活免疫应答起重要作用。近年发现Toll样受体在多种肿瘤的发生过程中起重要的调控作用。Toll样受体在肿瘤细胞中具有表达,并且Toll样受体信号诱导的促炎症反应是肿瘤发生的必要条件,但是有些Toll样受体的配体仍然表现出极强的抗肿瘤活性,目前,Toll样受体在肿瘤免疫中的机制研究已经成为Toll样受体作为药物靶点的临床应用的关键。本文对Toll样受体在肿瘤免疫中的机制进行综述。     

Toll样受体介导的肠道免疫研究进展

黏膜免疫系统的第一道防线——肠黏膜上皮,不但能区分和识别致病菌和共生菌,而且能启动适当的免疫应答。在机体正常情况下,肠黏膜上皮细胞（IEC）对肠道共生菌持耐受状态,维持肠道内环境的稳定。IEC能识别致病菌的危险信号,激活派伊尔结节,启动免疫应答。有关实验已证实肠黏膜上皮针对肠腔细菌呈“耐受”或“非耐受”状态,主要依赖于Toll样受体（TLRS）介导的信号转导通路。     

Toll样受体与抗真菌感染免疫

Toll样受体是一类保守的天然免疫识别受体家族,可识别众多微生物共有的保守模式分子——病原体相关分子模式,通过某些信号转导途径,激发机体先天性及获得性免疫应答,引起炎症介质的释放。数个真菌细胞壁成分可被Toll样受体识别,不同的白细胞介素1受体／Toll样受体超家族成员通过MyD88的相互作用,激活Toll样受体信号转导通路,从而诱导宿主抵抗真菌的攻击。     

靶向 Toll 样受体的免疫调节剂研究进展

Toll 样受体是一类相对保守的模式识别受体,可以识别损伤相关分子模式和病原相关分子模式,从而启动天然免疫应答,在天然免疫过程中发挥非常重要的作用。其介导的信号通路失调会引发各种炎症反应、癌症和自身免疫病等疾病。综述近年与 Toll 样受体有关的免疫调节剂的研究进展,并概括与之相关的疾病,为靶向 Toll 样受体的免疫调节剂的研发提供一定参考。     

Toll样受体在抗感染免疫中的作用

目前已确认的人类Toll样受体有10个,它们分别识 病原微生物不同的病原体相关分子特式结构,其中TLR9与细菌CpG-DNA关系的发现,受到人们普遍的重视和关注,本文简要地介绍细菌CpG基序与TLR9,鞭毛蛋白与TLR5和病毒与TLR5等的相互关系及其意义。     

Toll样受体的研究进展

Toll样受体是近几年发现的天然免疫受体,它们不仅能特异性地识别病原微生物的结构成分,激活天然免疫,同时也为激活获得性免疫提供共刺激信号。Toll样受体是天然免疫与获得性免疫之间的连接点。     

Toll 样受体与天然免疫

Toll样受体家族是一类模式识别受体,它介导了一个植物,昆虫,哺乳动物共同拥有的高度保守的信号通路。最近几年相继发现了多种人类Toll样受体以及相关的病原微生物配体,这些配体涵盖了病毒,细菌,真菌等微生物上多种保守的病原相关分子模式。可见Toll样受体在多种病原微生物及其产物的识别和免疫防御反应中有重要的作用。     

天然免疫进化中的无脊椎动物Toll样受体

Toll样受体（Toll-like receptors,TLR）（或Toll）通过与各种病原相关分子模式（pathogen associated molecular patterns,PAMP）的识别和特异结合,广泛参与各种天然免疫应答,目前已在线虫类、软体动物、节肢动物、棘皮动物及低等脊索类的后口动物等多种无脊椎动物中发现大量的TLR及同源蛋白.TLR在进化中高度保守,其功能随着动物进化中免疫机能的复杂化而多样化.这些研究成果将会不断加深对无脊椎动物天然免疫系统的起源、进化路线及其信号转导机制的认识.     

Toll样受体家族与天然免疫

Toll受体是近年来发现的跨膜信号传递受体蛋白,它在哺乳动物,昆虫及植物的信号转导通路中有类似的作用。TLR可选择性识别病原微生物而启动天然免疫,因此,它在宿主的天然免疫中具有重要作用。本文主要对TLR家族的研究进展及其在天然免疫中的作用加以综述。     

Advances in antibody-mediated immunity against Mycobacterium tuberculosis: implications for a novel vaccine strategy

Cell-mediated immunity is considered to be the major component of the host response against Mycobacterium tuberculosis, whereas antibody-mediated immunity historically has been considered inconsequential. In recent years, studies from several groups have challenged the traditional dogma and demonstrated that monoclonal antibodies can modify various aspects of mycobacterial infections. This review describes the experimental evidence supporting a role for antibodies in defense against mycobacterial infections and outlines future challenges to the field of antibody-mediated immunity against M. tuberculosis, with particular emphasis on the implications of these findings for a novel vaccine strategy.     

Tuberculosis patients co-infected with Mycobacterium bovis and Mycobacterium tuberculosis in an urban area of Brazil

In this cross-sectional study, mycobacteria specimens from 189 tuberculosis (TB) patients living in an urban area in Brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pncA gene and oxyR pseudogene analysis). Of these samples, 174 isolates simultaneously grew on Löwenstein-Jensen (LJ) and Stonebrink (SB)-containing media and presented phenotypic and molecular profiles of Mycobacterium tuberculosis, whereas 12 had molecular profiles of M. tuberculosis based on the DNA analysis of formalin-fixed paraffin wax-embedded tissue samples (paraffin blocks). One patient produced two sputum isolates, the first of which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, and the second of which only grew on SB media and presented phenotypic profiles of Mycobacterium bovis. One patient provided a bronchial lavage isolate, which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, but had molecular profiles of M. bovis from paraffin block DNA analysis, and one sample had molecular profiles of M. tuberculosis and M. bovis identified from two distinct paraffin blocks. Moreover, we found a low prevalence (1.6%) of M. bovis among these isolates, which suggests that local health service procedures likely underestimate its real frequency and that it deserves more attention from public health officials.     

耐药结核分枝杆菌潜伏-复发感染动物模型的研究进展

潜伏结核感染(latent tuberculosis infection,LTBI)复发是新发结核病的主要来源,其中耐药结核病所占比例较大,使耐药LTBI复发的防控成为结核病研究的重点。耐药结核分枝杆菌潜伏-复发感染动物模型是开展耐药结核病防控相关机制研究、抗耐药结核分枝杆菌药物和疫苗研究的基础。目前耐药结核分枝杆菌感染动物模型缺乏,而已有的结核分枝杆菌标准株H37Rv潜伏-复发感染模型存在缺陷,如小鼠模型的潜伏期荷菌量偏高、复发期变异大,而猴模型的潜伏期和复发期不可预测。模型的可控性差使其应用困难,且缺乏可用的免疫学评价指标,导致远期复发无法预测。因此,基于现有H37Rv潜伏-复发感染动物模型的制备方法,展望耐药结核分枝杆菌潜伏-复发感染动物模型可能存在的缺陷,通过选用新的抑菌剂和诱导剂,制备有稳定潜伏期、潜伏时长适中、复发起点和复发水平变异小的动物模型,是未来耐药结核分枝杆菌潜伏-复发感染动物模型研究的方向。     

Mycobacterium tuberculosis Controls MicroRNA-99b (miR-99b) Expression in Infected Murine Dendritic Cells to Modulate Host Immunity

Mycobacterium tuberculosis resides and replicates within host phagocytes by modulating host microbicidal responses. In addition, it suppresses the production of host protective cytokines to prevent activation of and antigen presentation by M. tuberculosis-infected cells, causing dysregulation of host protective adaptive immune responses. Many cytokines are regulated by microRNAs (miRNAs), a newly discovered class of small noncoding RNAs, which have been implicated in modulating host immune responses in many bacterial and viral diseases. Here, we show that miRNA-99b (miR-99b), an orphan miRNA, plays a key role in the pathogenesis of M. tuberculosis infection. We found that miR-99b expression was highly up-regulated in M. tuberculosis strain H37Rv-infected dendritic cells (DCs) and macrophages. Blockade of miR-99b expression by antagomirs resulted in significantly reduced bacterial growth in DCs. Interestingly, knockdown of miR-99b in DCs significantly up-regulated proinflammatory cytokines such as IL-6, IL-12, and IL-1β. Furthermore, mRNA and membrane-bound protein data indicated that inhibition of miR-99b augments TNF-α and TNFRSF-4 production. Thus, miR-99b targets TNF-α and TNFRSF-4 receptor genes. Treatment of anti-miR-99b-transfected DCs with anti-TNF-α antibody resulted in increased bacterial burden. Thus, our findings unveil a novel host evasion mechanism adopted by M. tuberculosis via miR-99b, which may open up new avenues for designing miRNA-based vaccines and therapies.     

Toll样受体4对动脉粥样硬化发生、发展的研究进展

动脉粥样硬化（atherosclerosis,AS）是多种细胞、炎性介质参与形成的慢性炎症性疾病。Toll样受体家族（Toll like receptors,TLRs）中的TLR4是机体重要的诱导分泌多种炎性因子的模式识别受体。现有证据表明,TLR4不仅产生多种炎性因子诱发血管炎症反应,而且促进AS斑块形成和发展,造成斑块不稳定,甚至破裂,对AS的发生、发展具有重要作用。因此,了解TLR4对AS的影响有助于发现新的治疗靶点和对策。主要对TLR4在AS发病机制和易损斑块发展中的作用进行综述。     

结核分枝杆菌的致病机理

结核病仍是全球健康的主要威胁,其致病菌结核分枝杆菌的致闰机理与众不同。脂类代谢在致病中具有重要的作用。巨噬细胞被入侵的细菌修的机理也是研究细菌持续感染致病的重要突破点,研究细菌的致病机理可以为开发新的疫苗和治疗药物奠定坚实的基础。     

结核分枝杆菌对异烟肼耐药的分子机制

抗结核一线药物异烟肼是应用最广泛的抗结核药物之一,自1952年应用于临床以来,异烟肼就成了治疗结核和潜在感染的基础药物.有报道,我国异烟肼耐药已排在首位.结核分枝杆菌对异烟肼耐药的分子机制十分复杂,涉及katG、inhA、kasA、ndh、axyR等多种基因,本研究仅就此方面的研究作一综述.     

Effect of Immunization of Cats with Isospora felis and BCG on Immunity to Reexcretion of Toxoplasma gondii Oocysts*

SYNOPSIS. The effect of pretreatment with Isospora felis and bacillus Calmette-Guérin (BCG) on the reexcretion of Toxoplasma gondii occysts was studied in 16 coccidia-free cats. The following conclusions were drawn: (A) Chronically T. gondii-infected cats reexcreted T. gondii oocysts after superinfection with I. felis, and this reexcretion was prevented in cats infected with I. felis before T. gondii infection. (B) Administration of BCG before Toxoplasma infection had no apparent effect on the outcome of the infection.     

Animal models to study Mycobacterium tuberculosis and HIV co-infection

Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV coinfection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV coinfection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.