病原微生物毒力因子与宿主细胞信号通路相互作用研究进展

病原微生物与宿主的相互作用是感染性疾病发生的基础,涉及病原微生物在宿主体内的生存、复制、传播及致病等多个过程。病原菌在进化过程中发展了多种策略以攻击宿主,其中最重要的一种方式就是通过毒力蛋白影响宿主细胞信号通路,病原菌可以通过多种方式阻断宿主信号通路的激活,如乙酰化、β消除等。研究病原体与宿主细胞相互作用的规律,有望发现具有广谱作用的传染病防治药物。我们就病原体通过信号转导影响细胞功能的研究进展做简要综述。     

隐球菌形态学变化及其致病机制

致病真菌在与宿主相互作用过程中可能发生形态学变化,如菌丝形成.这种形态学变化有利于病原菌适应不同的外界环境,使其在宿主体内生存.外有荚膜包裹的隐球菌是隐球菌病的致病真菌.该菌可通过孢子吸人方式侵入宿主体内,其后又能通过增加自身荚膜厚度和形成巨大菌体来抵抗和逃避宿主的免疫防御功能.对隐球菌形态学变化意义的理解,有助于了解该病的致病机制,从而推动临床诊治发展.     

猪链球菌2型与宿主细胞体外相互作用研究进展

猪链球菌2型(Streptococcus suis serotype2,SS2)是一种世界范围内的引起猪链球菌病的重要的人兽共患病原菌,人感染SS2后多呈现败血症型和脑膜炎型。2005年猪链球菌在我国四川省的感染暴发和近年来不断出现的零散病例给我国的公共卫生和食品安全带来了威胁,但迄今为止,对SS2致病机制研究尚不够深入。SS2的致病过程和宿主细胞相互作用密切相关,SS2-体外宿主细胞相互作用模型的建立对于揭示SS2致病分子机理具有重要的意义。目前的研究报道主要是从猪链球菌黏附与侵袭上皮细胞或内皮细胞、猪链球菌抗吞噬细胞的吞噬和猪链球菌激活免疫细胞炎症反应方面研究猪链球菌与宿主细胞的相互作用,但与其他常致病性链球菌如化脓性链球菌和肺炎链球菌相比,有些SS2-体外宿主细胞相互作用模型还缺乏统一的标准,由于感染模型的实验参数不尽相同得到结果也有所不同。本文对近年来猪链球菌2型与宿主细胞体外相互作用及其致病机理研究进展作一综述。     

病原菌逃避单核-巨噬细胞杀灭策略的研究进展

单核-巨噬细胞具有强大的吞噬功能,在机体固有免疫和适应性免疫中均发挥着重要作用,可有效保护宿主免受多种致病菌的感染。病原菌在与宿主单核-巨噬细胞的长期相互作用过程中,逐渐形成多种逃避杀灭的有效策略,得以在宿主体内存活并增殖。本文从病原菌抗巨噬细胞吞噬作用、抗巨噬细胞内吞噬溶酶体降解作用、诱导和抑制巨噬细胞凋亡或坏死4个方面,综述近年来国内、外关于病原菌逃避单核-巨噬细胞杀灭策略的研究进展。     

侵袭性致病菌对宿主细胞信号传递通路及细胞骨架功能的利用

<正>引言 病原菌已形成多种机制与宿主组织相互作用。这种现象多见于病原菌对肠上皮细胞的入侵。在肠上皮细胞内病原菌数量很多,它们特别善于利用宿主的细胞功能为自己服务。本文以上皮细胞与随意进入细胞内的病原菌之间的相互作用为例,着重介绍了病原菌对宿主细胞某些机能的利用。     

衣原体与宿主细胞相互作用研究进展

衣原体是专性细胞内寄生、有独特发育周期的原核细胞型微生物,为了建立有益于病原体复制的细胞内环境,衣原体依赖于它们操纵宿主细胞内环境的能力,并且进化成了与宿主细胞相互作用的复杂机制,本文从感染衣原体后宿主细胞变化、免疫反应及蛋白质组改变等几个方面简要综述了衣原体与宿主细胞相互作用的最新进展,为进一步研究衣原体致病机制提供参考。     

病原菌作用于细胞焦亡的策略:盾-矛之争

焦亡是一种细胞程序性死亡的形式,其特征表现为细胞的裂解并伴随细胞因子、损伤和病原体相关的分子模式的释放.细胞焦亡能够促进炎症免疫反应发生,消除细胞内的病原菌,在细胞抵御病原菌感染过程中发挥重要作用.但是,在长期的军备竞赛中,病原体已进化出抑制宿主细胞焦亡的机制,以增强它们生存和致病的能力.本文从细胞焦亡的分子机制及其在宿主防御中的作用,以及病原菌抵御宿主细胞焦亡的策略等方面进行了综述,将有助于人们进一步了解和探索细菌病原体和细胞焦亡相互作用的机制,并为将来开发基于细胞焦亡抵抗病原体感染的新药提供思路.     

分泌型蛋白介导白念珠菌与宿主相互作用分子机制的研究进展

白念珠菌是人类最常见的条件性致病真菌之一,主要定植于人体粘膜表面。在白念珠菌与宿主相互作用过程中,分泌型蛋白起着非常重要的作用。针对分泌蛋白功能及其作用机理的研究有助于阐明白念珠菌致病分子机制,并为诊断、预防和治疗真菌感染提供新的理论策略。本文综述了白念珠菌分泌型蛋白在介导病原与宿主相互作用分子机制方面的最新研究进展,概括了分泌蛋白在组织侵入损伤、营养获取、细胞壁维持以及免疫逃避等方面的功能,同时对未来值得重点关注的研究方向进行了探讨。     

伤寒沙门菌对宿主细胞磷酸肌醇的调节与利用

宿主细胞的磷酸肌醇是细胞信号通路中的重要成分,参与许多细胞内过程(如细胞生长与分化、肌动蛋白的组装、细胞运动、细胞死亡、膜运动、葡萄糖转运等)的调节,是细胞生物学中极为重要的一组分子.近来的研究表明,病原菌(尤其是胞内寄生菌)可以利用磷酸肌醇信号通路,颠覆宿主细胞的功能.本文综述伤寒沙门菌对宿主细胞磷酸肌醇信号通路的调节与利用,有利于了解胞内寄生菌的寄生和致病机制.同时,细菌与宿主细胞相互作用的模型给人们提供了重要的手段来破解真核细胞内的复杂信号传导之谜.     

结核分枝杆菌与巨噬细胞相互作用的研究进展

结核分枝杆菌（Mycobacterium tuberculosis,MTB）是一种典型的胞内致病菌,巨噬细胞是MTB在体内的主要宿主细胞。巨噬细胞具有强大的吞噬功能,在机体固有免疫和适应性免疫中均发挥着重要作用,可有效保护宿主免受结核分枝杆菌的感染。MTB在与宿主巨噬细胞的长期相互作用过程中,逐渐形成多种逃避杀灭的有效策略,得以在宿主体内存活并增殖。该文从巨噬细胞抗MTB感染及MTB逃避巨噬细胞杀灭两个方面综述国内外的研究进展。     

肠道病毒71型与天然免疫系统相互作用的研究进展

肠道病毒71型(enterovirus 71,EV71)为小RNA病毒科肠道病毒属成员,是引起手足口病的主要病原体之一。EV71流行广泛,其感染可引发中枢神经系统疾病,并造成重症手足口病,给公共卫生安全带来极大挑战。EV71的致病机制与病毒和宿主天然免疫系统的相互作用关系密切,涉及病毒逃逸干扰素反应、病毒抑制核因子κB(nuclear factorκB,NF-κB)信号通路及病毒与天然免疫细胞相互作用等多个环节。本文就近年来EV71与宿主天然免疫系统相互作用的研究进展进行综述。     

Host–pathogen interactions: a proteomic view

Host–pathogen interactions reflect the balance of host defenses and pathogen virulence mechanisms. Advances in proteomic technologies now afford opportunities to compare protein content between complex biologic systems ranging from cells to animals and clinical samples. Thus, it is now possible to characterize host–pathogen interactions from a global proteomic view. Most reports to date focus on cataloging protein content of pathogens and identifying virulence-associated proteins or proteomic alterations in host response. A more in-depth understanding of host–pathogen interactions has the potential to improve our mechanistic understanding of pathogenicity and virulence, thereby defining novel therapeutic and vaccine targets. In addition, proteomic characterization of the host response can provide pathogen-specific host biomarkers for rapid pathogen detection and characterization, as well as for early and specific detection of infectious diseases. A review of host–pathogen interactions focusing on proteomic analyses of both pathogen and host will be presented. Relevant genomic studies and host model systems will be also be discussed.     

Host-pathogen interactions: a proteomic view

Host-pathogen interactions reflect the balance of host defenses and pathogen virulence mechanisms. Advances in proteomic technologies now afford opportunities to compare protein content between complex biologic systems ranging from cells to animals and clinical samples. Thus, it is now possible to characterize host-pathogen interactions from a global proteomic view. Most reports to date focus on cataloging protein content of pathogens and identifying virulence-associated proteins or proteomic alterations in host response. A more in-depth understanding of host-pathogen interactions has the potential to improve our mechanistic understanding of pathogenicity and virulence, thereby defining novel therapeutic and vaccine targets. In addition, proteomic characterization of the host response can provide pathogen-specific host biomarkers for rapid pathogen detection and characterization, as well as for early and specific detection of infectious diseases. A review of host-pathogen interactions focusing on proteomic analyses of both pathogen and host will be presented. Relevant genomic studies and host model systems will be also be discussed.     

The intracellular pathogen concept

The intracellular pathogen concept classifies pathogenic microbes on the basis of their site of replication and dependence on host cells. This concept played a fundamental role in establishing the field of cellular microbiology, founded in part by Dr. Pascale Cossart, whose seminal contributions are honored in this issue of Molecular Microbiology. The recognition that microbes can access and replicate in privileged compartments within host cells has led to many new and fruitful lines of investigation into the biology of the cell and mechanisms of cell-mediated immunity. However, like any scientific concept, the intracellular pathogen concept can become a dogma that constrains thinking and oversimplifies complex and dynamic host–pathogen interactions. Growing evidence has blurred the distinction between “intracellular” and “extracellular” pathogens and demonstrated that many pathogens can exist both within and outside of cells. Although the intracellular pathogen concept remains useful, it should not be viewed as a rigid classification of pathogenic microbes, which exhibit remarkable variation and complexity in their behavior in the host.     

Simulated microgravity perturbs actin polymerization to promote nitric oxide-associated migration in human immortalized Eahy926 cells

Apicomplexan parasites obligatorily invade and multiply within eukaryotic cells. Phylogenetically, they are related to a group of algae which, during their evolution, have acquired a secondary endosymbiont. This organelle, which in the parasite is called the apicoplast, is highly reduced compared to the endosymbionts of algae, but still contains many plant-specific biosynthetic pathways. The malaria parasite Plasmodium falciparum infects mammalian erythrocytes which are devoid of intracellular compartments and which largely lack biosynthetic pathways. Despite the limited resources of nutrition, the parasite grows and generates up to 32 merozoites which are the infectious stages of the complex life cycle. A large part of the intra-erythrocytic development takes place in the so-called parasitophorous vacuole, a compartment which forms an interface between the parasite and the cytoplasm of the host cell. In the course of parasite growth, the host cell undergoes dramatic alterations which on one hand contribute directly to the symptoms of severe malaria and which, on the other hand, are also required for parasite survival. Some of these alterations facilitate the acquisition of nutrients from the extracellular environment which are not provided by the host cell. Here, we describe the cell biologically unique interactions between an intracellular eukaryotic pathogen and its metabolically highly reduced host cell. We further discuss current models to explain the appearance of pathogen-induced novel physiological properties in a host cell which has lost its genetic programme.     

Global analysis of Arabidopsis/downy mildew interactions reveals prevalence of incomplete resistance and rapid evolution of pathogen recognition

Interactions between Arabidopsis thaliana and its native obligate oomycete pathogen Hyaloperonospora arabidopsidis (Hpa) represent a model system to study evolution of natural variation in a host/pathogen interaction. Both Arabidopsis and Hpa genomes are sequenced and collections of different sub-species are available. We analyzed ～400 interactions between different Arabidopsis accessions and five strains of Hpa. We examined the pathogen's overall ability to reproduce on a given host, and performed detailed cytological staining to assay for pathogen growth and hypersensitive cell death response in the host. We demonstrate that intermediate levels of resistance are prevalent among Arabidopsis populations and correlate strongly with host developmental stage. In addition to looking at plant responses to challenge by whole pathogen inoculations, we investigated the Arabidopsis resistance attributed to recognition of the individual Hpa effectors, ATR1 and ATR13. Our results suggest that recognition of these effectors is evolutionarily dynamic and does not form a single clade in overall Arabidopsis phylogeny for either effector. Furthermore, we show that the ultimate outcome of the interactions can be modified by the pathogen, despite a defined gene-for-gene resistance in the host. These data indicate that the outcome of disease and disease resistance depends on genome-for-genome interactions between the host and its pathogen, rather than single gene pairs as thought previously.     

The role of the ER and cytoskeleton in plant viral trafficking

Plant viruses spread from cell to cell via plasmodesmata, which bridge the rigid cell wall and connect adjacent cells. The spread of infection is aided by interactions between the virus and the host components. These interactions have been intensively studied to understand the crosstalk between pathogen and host. The use of green fluorescent protein has shed new light on the close association between viral movement proteins and elements of the cytoskeleton and the endomembrane system.     

Prediction of protein-protein interactions between human host and a pathogen and its application to three pathogenic bacteria

Molecular understanding of disease processes can be accelerated if all interactions between the host and pathogen are known. The unavailability of experimental methods for large-scale detection of interactions across host and pathogen organisms hinders this process. Here we apply a simple method to predict protein-protein interactions across a host and pathogen organisms. We use homology detection approaches against the protein-protein interaction databases, DIP and iPfam in order to predict interacting proteins in a host-pathogen pair. In the present work, we first applied this approach to the test cases involving the pairs phage T4 -Escherichia coli and phage lambda -E. coli and show that previously known interactions could be recognized using our approach. We further apply this approach to predict interactions between human and three pathogens E. coli, Salmonella enterica typhimurium and Yersinia pestis. We identified several novel interactions involving proteins of host or pathogen that could be thought of as highly relevant to the disease process. Serendipitously, many interactions involve hypothetical proteins of yet unknown function. Hypothetical proteins are predicted from computational analysis of genome sequences with no laboratory analysis on their functions yet available. The predicted interactions involving such proteins could provide hints to their functions.     

Dendritic cells and C-type lectin receptors: coupling innate to adaptive immune responses

Dendritic cells (DCs) have an important function in the initiation and differentiation of immune responses, linking innate information to tailored adaptive responses. Depending on the pathogen invading the body, specific immune responses are built up that are crucial for eliminating the pathogen from the host. Host recognition of invading microorganisms relies on evolutionarily ancient, germline-encoded pattern recognition receptors (PRRs) that are highly expressed on the cell surface of DCs, of which the Toll-like receptors (TLRs) are well characterized and recognize bacterial or viral components. Moreover, they bind a variety of self-proteins released from damaged tissues including several heat-shock proteins. The membrane-associated C-type lectin receptors (CLRs) recognize glycan structures expressed by host cells of the immune system or on specific tissues, which upon recognition allow cellular interactions between DCs and other immune or tissue cells. In addition, CLRs can function as PRRs. In contrast to TLRs, CLRs recognize carbohydrate structures present on the pathogens. Modification of glycan structures on pathogens to mimic host glycans can thereby alter CLR interactions that subsequently modifies DC-induced polarization. In this review, we will discuss in detail how specific glycosylation of antigens can dictate both the innate and adaptive interactions that are mediated by CLRs on DCs and how this balances immune activation and inhibition of DC function.