细胞自噬的研究进展

自噬(autophagy)是广泛存在于真核细胞中的细胞生物学行为,是一种溶酶体依赖性降解途径,是细胞进行自我保护的一种重要机制,对于维持细胞存活、更新、物质再利用和内环境稳定中起着重要作用。近年来,诸多的研究表明,细胞自噬积极参与多种病原体感染宿主动物/细胞的过程,而且在不同病原体的感染过程中所起的作用不尽相同。本文从自噬的发现及分类、发生过程、自噬调控基因、检测方法和自噬与病原体相互关系进行了综述。     

细胞自噬在细小病毒感染中的作用机制研究进展

自噬是真核细胞中常见的一种保守的溶酶体分解代谢途径，对宿主代谢至关重要。其主要功能包括饥饿时的能量守恒、细胞器的循环和长寿蛋白质的正常周转。自噬在清除细胞内病原体方面起着关键作用，很可能是一种原始的内在细胞防御机制。最近的研究表明，自噬在病毒感染过程中起着复杂的多向作用，它不仅保留了降解细胞内病原体的能力，还具有增强和微调抗病毒免疫反应的功能。然而，一些病毒也进化出各种机制以逃避自噬降解，促进其自身的复制和释放。本文综述了自噬与病毒感染相互作用的研究进展，强调了自噬与细小病毒之间的分子相互作用，为抗病毒药物及疫苗研发提供理论基础，从而为细小病毒的防控提供新思路。     

细胞自噬与胞内病原体感染相互作用的研究进展

作为先天性免疫的一部分,自噬在胞内病原体感染过程中发挥着“双刃剑”的作用,一方面自噬可抑制、消灭胞内感染病原体,保护机体免受病原体的侵害;另一方面一些胞内病原体可抑制、阻断自噬的发生或成熟,甚至利用自噬逃避机体的免疫机制,利于其在体内的存活、增殖。作者从细胞自噬与胞内病原体之间的相互关系着手,对自噬在胞内病原体感染过程中所发挥的作用进行综述。     

ssRNA病毒侵染宿主细胞与细胞抗病毒作用的研究进展

单链RNA(single-strandRNA,ssRNA)病毒是感染人和动物的主要病原体之一，部分ssRNA病毒感染宿主后会对宿主产生致命的影响，也有部分ssRNA病毒进入宿主后不会引发明显的病变和临床症状。ssRNA病毒与宿主细胞之间的感染与抗病毒所产生的炎症反应、细胞凋亡、细胞溶酶体/自噬应答均是动物机体在ssRNA病毒入侵后产生的一系列抗病毒活动。大量研究解析了ssRNA病毒与宿主细胞之间的相互关系，但仍有许多未知领域阻碍着抗ssRNA病毒研究的前进步伐。基于已公开发表的研究论文，笔者梳理并分析了ssRNA病毒与被侵染细胞之间的相互关系，为后续研究ssRNA病毒与宿主细胞应答反应提供理论支持。     

细胞自噬与猪流行性腹泻病毒相互作用的研究进展

猪流行性腹泻病毒（PEDV）是冠状病毒科甲型冠状病毒属的一种有囊膜的单股正链RNA病毒,对全世界养猪业造成了巨大的损失。PEDV与宿主之间的致病机制和免疫调节相互作用仍不清楚。有研究表明冠状病毒可以诱导细胞发生自噬,并且与病毒的复制有着密切的联系,病毒与细胞自噬之间的关系十分复杂,虽然病毒感染与细胞自噬之间的关系研究比较广泛,但细胞自噬在PEDV感染中的作用报道较少。研究PEDV与细胞自噬的相互作用可以加速对PEDV感染入侵机制的理解,为未来研究病毒治疗和抗病毒药物提供新的思路。 [关键词] 猪流行性腹泻病毒|细胞自噬|相互作用     

细胞自噬与猪流行性腹泻病毒相互作用的研究进展

猪流行性腹泻病毒（PEDV）是冠状病毒科甲型冠状病毒属的一种有囊膜的单股正链RNA病毒，对全世界养猪业造成了巨大的损失。PEDV与宿主之间的致病机制和免疫调节相互作用仍不清楚。有研究表明冠状病毒可以诱导细胞发生自噬，并且与病毒的复制有着密切的联系，病毒与细胞自噬之间的关系十分复杂，虽然病毒感染与细胞自噬之间的关系研究比较广泛，但细胞自噬在PEDV感染中的作用报道较少。研究PEDV与细胞自噬的相互作用可以加速对PEDV感染入侵机制的理解，为未来研究病毒治疗和抗病毒药物提供新的思路。     

PRRSV感染对细胞自噬与Th1/Th2细胞极化影响的研究进展

猪繁殖与呼吸综合征(PRRS)是一种急性、高度接触性传染病,严重危害着养猪业的健康发展。目前的药物和疫苗不能有效防治该病,因此研究猪繁殖与呼吸综合征病毒(PRRSV)的致病机制具有重要意义。自噬是最新发现的一种细胞维持生存的途径,它是通过降解大分子物质及回收受损细胞来维持细胞内环境稳态变化的一种生理现象,在病原微生物感染过程中发挥关键的调控作用。研究表明,PRRSV感染能够诱导细胞自噬,而自噬参与调控Th1/Th2细胞平衡,Th1/Th2细胞因子极化在宿主防御病原感染中起着至关重要的作用。因此,文章对PRRSV感染、Th1/Th2细胞极化与细胞自噬的相关性,以及Th1/Th2细胞极化与PRRSV的免疫相关性进行综述,以期更加深入地了解PRRSV致病机制。     

自噬与A型流感病毒感染

自噬是广泛存在于真核细胞内的新陈代谢过程,对于维持细胞自稳具有关键作用。在病毒感染过程中,自噬表现出两面性,既可被利用来促进病毒复制,又在宿主抗感染免疫应答中发挥重要作用。论文以严重危害畜禽生产和人类健康的A型流感病毒为例,论述了细胞自噬与病毒感染及在宿主免疫应答过程中的相互关系,旨在进一步深入理解A型流感病毒的致病分子机制,为抗流感病毒感染的相关研究提供参考。     

自噬通路及其在顶复门原虫入侵发育中的作用

自噬(autophagy)是细胞通过降解自身大分子物质或破损细胞器等来维持胞内稳态的一种平衡机制.近年来在顶复门原虫与宿主细胞相互作用研究中发现,顶复门原虫不但可诱导宿主细胞产生自噬并启动天然免疫途径清除寄生虫,亦可进化出独特的机制来抵抗宿主细胞自噬甚至利用其为自身生长提供条件.不同种类顶复门原虫与宿主细胞互作方式不同...     

布鲁氏菌的胞内生存机制研究进展

布鲁氏菌的感染周期和致病能力主要取决于其在吞噬细胞内的生存能力。布鲁氏菌入侵宿主细胞后,会经历多阶段复杂的细胞内循环过程。它们通过Ⅳ型分泌系统(T4SS)的介导依次通过内吞层,分泌层和自噬区,并发挥其功能。T4SS启动子调节一系列宿主功能和机制,首先促进最初的内体样布氏小体(eBCV)转化为融合宿主内质网的复制细胞器(rBCV),然后转化为自噬相关囊泡(aBCV)完成布鲁氏菌释放。论文详细介绍和讨论了目前对布鲁氏菌细胞内循环过程和相关分子机制研究进展,论述了T4SS功能的表达在内体阶段的作用,自噬在rBCV生成和aBCV形成中的作用以及T4SS介导的rBCV生成和布鲁氏菌调节宿主分泌转运机制的重要性。     

Engagement of integrins as a cellular route of invasion by bacterial pathogens

Integrins are heterodimeric receptors that mediate important cell functions, including cell adhesion, migration and tissue organisation. These transmembrane receptors regulate the direct association of cells with each other and with extracellular matrix proteins. However, by binding their ligands, integrins provide a transmembrane link for the bidirectional transmission of mechanical forces and biochemical signals across the plasma membrane. Interestingly, several of this family of receptors are exploited by pathogens to establish contact with the host cells. Hence, microbes subvert normal eukaryotic cell processes to create a specialised niche which allows their survival. This review highlights the fundamental role of integrins in bacterial pathogenesis.     

Mixed infections of rotaviruses and Campylobacter jejuni in Caco-2 cells

A mixed infection with rotavirus and 3 different Campylobacter jejuni strains was analysed in Caco-2 cells, a cell line highly susceptible to these pathogens. The results obtained showed no influence of the virus preinfection on the Campylobacter jejuni adhesion or internalisation in Caco-2 cells. Confocal laser scanning microscopy of mixed infected cells confirmed these results. The data from the present study indicate that specific rather than nonspecific mechanisms are involved in the interaction between rotavirus, campylobacter and host cells.     

Secretion of multi-protein migratory complex induced by Toxoplasma gondii infection in macrophages involves the uPA/uPAR activation system

Toxoplasmosis is a world wide spread zoonosis caused by Toxoplasma gondii, an obligate intracellular parasite that is able to disseminate into deep tissues and cross biological barriers, reaching immunoprivileged sites such as the brain and retina. The parasite is able to infect macrophages and dendritic cells for dispersal throughout the body. However, the molecular mechanisms or outcomes of the subversion of the host cell are largely unknown. Recently our group established that metalloproteinases are involved in migration of infected macrophages. Herein, we evaluated the recruitment of host invasive machinery components in T. gondii infected murine macrophages. We showed by immunoprecipitation assays that MMP-9, CD44 TIMP-1 and uPAR were secreted as a multi-protein complex by infected macrophages. Zymographic analysis revealed that MMP-9 was present in its pro- and active form. Moreover, inhibition of uPA/uPAR pathway by PAI-1 decreased secretion of MMP-9 active forms, as well those associated to uPAR and TIMP-1, but not to CD44. Data presented here suggest that MMP-9 is secreted as a multiprotein complex by T. gondii infected macrophages, similar to that observed in metastatic cells. We further speculate that uPA/uPAR system is involved in the expression/secretion of complexes containing active MMP-9 forms.     

猪外周血T淋巴细胞增殖反应MTT检测方法的建立

T细胞增殖反应是宿主T细胞识别病原的结果,也是宿主细胞免疫应答的重要指标之一。为了便于检测猪群在病原感染或者疫苗免疫过程中产生的细胞免疫应答,本研究应用MTT法建立了体外检测猪外周血T细胞增殖反应的研究方法。通过密度梯度离心法从外周血分离得到外周血单个核细胞（PBMC）,然后利用单核细胞和淋巴细胞不同的生长特性（贴壁与否）,弃掉贴壁的单核细胞,获得外周血淋巴细胞(PBL)。外周血淋巴细胞的流式分析结果显示,分离获得的PBL中T细胞所占比例达到了80%以上。应用MTT法分析了非特异性刺激物刀豆蛋白A（ConA）的浓度和细胞培养密度对T细胞增殖的影响。结果显示,ConA的工作浓度为5 μg/mL、细胞培养密度为2×106/mL时T细胞的增殖反应最强烈。本研究所建立的猪外周血T细胞增殖反应检测法可以为研究猪针对病原或疫苗的细胞免疫反应提供参考。     

Molecular events involved in cellular invasion by Ehrlichia chaffeensis and Anaplasma phagocytophilum

Ehrlichia chaffeensis and Anaplasma phagocytophilum are obligatory intracellular bacteria that preferentially replicate inside leukocytes by utilizing biological compounds and processes of these primary host defensive cells. These bacteria incorporate cholesterol from the host for their survival. Upon interaction with host monocytes and granulocytes, respectively, these bacteria usurp the lipid raft domain containing GPI-anchored protein to induce a series of signaling events that result in internalization of the bacteria. Monocytes and neutrophils usually kill invading microorganisms by fusion of the phagosomes containing the bacteria with granules containing both antimicrobial peptides and lysosomal hydrolytic enzymes and/or through sequestering vital nutrients. However, E. chaffeensis and A. phagocytophilum alter vesicular traffic to create a unique intracellular membrane-bound compartment that allows their replication in seclusion from lysosomal killing. These bacteria are quite sensitive to reactive oxygen species (ROS), so in order to survive in host cells that are primary mediators of ROS-induced killing, they inhibit activation of NADPH oxidase and assembly of this enzyme in their inclusion compartments. Moreover, host phagocyte activation and differentiation, apoptosis, and IFN-γ signaling pathways are inhibited by these bacteria. Through reductive evolution, lipopolysaccharide and peptidoglycan that activate the innate immune response, have been eliminated from these gram-negative bacteria at the genomic level. Upon interaction with new host cells, bacterial genes encoding the Type IV secretion apparatus and the two-component regulatory system are up-regulated to sense and adapt to the host environment. Thus dynamic signal transduction events concurrently proceed both in the host cells and in the invading E. chaffeensis and A. phagocytophilum bacteria for successful establishment of intracellular infection. Several bacterial surface-exposed proteins and porins are recently identified. Further functional studies on Ehrlichia and Anaplasma effector or ligand molecules and cognate host cell receptors will undoubtedly advance our understanding of the complex interplay between obligatory intracellular pathogens and their hosts. Such data can be applied towards treatment, diagnosis, and control of ehrlichiosis and anaplasmosis.     

病毒感染细胞过程中caspases介导的病毒蛋白自剪切研究概况

很多宿主细胞在病毒感染下通常会启动caspases通路凋亡途径导致细胞死亡,避免病毒的进一步扩增和传播.但最近的一些研究表明,病毒能利用激活的caspase蛋白酶对自身(非)结构蛋白进行特异性剪切,以利于病毒在细胞内的复制或参与病毒或宿主其他基因的转录调控等过程.作为一个病毒与宿主细胞相互作用关系的新的研究领域,论文对...     

肥大细胞在机体防御反应中的作用

肥大细胞的研究主要集中在过敏性痰病中,肥大细胞在机体抵御病原体感染中发挥着重要作用.肥大细胞除具有识别、吞噬并杀灭病原微生物的功能外,尚能加工、递呈抗原和调节免疫反应.肥大细胞有针对病原信号的特异性受体系统和介质.深入阐明肥大细胞在细菌和病毒感染中的作用和机制,不仅为天然免疫的研究开辟一个新领域,而且对感染性疾病的防治也有重要意义.     

Endothelial cells as active participants in veterinary infections and inflammatory disorders

Endothelial cells were once viewed as relatively inert cells lining the vasculature. They are now recognized as active and responsive regulators of coagulation, platelet adhesion, fluid homeostasis, wound healing, leukocyte extravasation and vascular tone. Endothelial cells play a key role in the host response to infectious agents by regulating leukocyte trafficking, producing inflammatory cytokines and presenting antigen in association with major histocompatibility class II (MHC II) molecules. A number of infectious agents have a tropism for endothelial cells. Infection of endothelial cells can promote thrombosis, vascular leakage, and increased adherence and emigration of leukocytes. Furthermore, activation of a systemic inflammatory response, in the absence of direct endothelial cell infection, can also lead to endothelial cell dysfunction. The purpose of this review is to highlight the interactions between endothelial cells and infectious or inflammatory agents that contribute to coagulation disturbances, vasculitis and edema. A select group of viral and bacterial pathogens will be used as examples to demonstrate how endothelial cell dysfunction contributes to the pathogenesis of infectious and inflammatory disorders.     

The biological and practical significance of antigenic variability in protective T cell responses against Theileria parva

The evolution of antigenically distinct pathogen strains that fail to cross-protect is well documented for pathogens controlled primarily by humoral immune responses. Unlike antibodies, which recognise native proteins, protective T cells can potentially recognise epitopes in a variety of proteins that are not necessarily displayed on the pathogen surface. Moreover, individual hosts of different MHC genotypes generally respond to different sets of epitopes. It is therefore less easy to envisage how strain restricted immunity can arise for pathogens controlled by T cell responses, particularly in antigenically complex parasites. Nevertheless, strain restricted immunity is clearly a feature of a number of parasitic infections, where immunity is known to be mediated by T cell responses. One such parasite is Theileria parva which induces potent CD8 T cell responses that play an important role in immunity. CD8 T cells specific for parasitized lymphoblasts exhibit strain specificity, which appears to correlate with the ability of parasite strains to cross-protect. Studies using recently identified T. parva antigens recognised by CD8 T cells have shown that the strain restricted nature of immunity is a consequence of the CD8 T cell response in individual animals being focused on a limited number of dominant polymorphic antigenic determinants. Responses in animals of different MHC genotypes are often directed to different parasite antigens, indicating that, at the host population level, a larger number of parasite proteins can serve as targets for the protective T cell response. Nevertheless, the finding that parasite strains show overlapping antigenic profiles, probably as a consequence of sexual recombination, suggests that induction of responses to an extended but limited set of antigens in individual animals may overcome the strain restricted nature of immunity.