Innate immunity against viruses

Viruses are obligate parasites which are able to infect cells of all living organisms. Multiple antiviral defense mechanisms have appeared early in evolution of the immune system. Higher vertebrates have the most complex antiviral immunity which is based on both innate and adoptive immune responses. However, majority of living organisms, including plants and invertebrates, rely exclusively on innate immune mechanisms for protection against viral infections. There are some striking similarities in several components of the innate immune recognition between mammals, plants and insects, rendering these signaling cascades as highly conserved in the evolution of the immune system. This review summarizes recent advances in the field of innate immune recognition of viruses, with particular interest on pattern-recognition receptors.     

Innate mechanisms of viral recognition

Viruses are obligate parasites which can infect cells of all living organisms. Multiple antiviral defense mechanisms appeared early in the evolution of the immune system. Higher vertebrates possess the most complex antiviral immunity based on both innate and adoptive immune responses. However, a majority of living organisms, including plants and invertebrates, rely exclusively on innate immune mechanisms for protection against viral infections. There are some striking similarities in several components of innate immune recognition in mammals, plants, and insects suggesting that these signaling cascades are highly conserved in the evolution of the immune system. This review summarizes recent advances in the field of innate immune recognition of viruses, with a focus on pattern-recognition receptors.     

昆虫天然免疫相关基因研究进展

在长期进化过程中,昆虫形成了强大的天然免疫防御系统,即体液免疫和细胞免疫。体液免疫主要包括Toll、IMD和JAK/STAT 3条信号通路,通过信号转导及免疫途径调控免疫相关基因的表达,诱导产生抗菌肽和其他效应分子。细胞免疫由血细胞介导,主要完成对病原物的包裹、吞噬和集结等。近年来,昆虫基因组学快速发展,通过生物信息学等方法从昆虫基因组数据中已鉴定到大量免疫相关基因,对这些基因的研究加深了人们对昆虫天然免疫分子机制的认识和理解。根据基因功能,免疫相关基因分为识别、信号转导、调制器、效应分子、黑化反应、RNA干扰和其他基因等7类,这些基因通过互作来调控体液免疫和细胞免疫。本文对昆虫免疫相关基因的分类、功能及家族进化等方面的研究成果进行总结,并对今后昆虫免疫的研究重点进行了展望,以期为昆虫免疫分子机制的研究及开发新的害虫防治策略提供依据。     

Toll-like receptors and corneal innate immunity

The ocular surface is constantly exposed to a wide array of microorganisms. The ability of the cornea to recognize pathogens as foreign and eliminate them is critical to retain its transparency, hence preservation of sight. In the eye, as in other parts of the body, the early response against invading pathogens is provided by innate immunity. Corneal innate immune system uses a series of pattern recognition receptors to detect the presence of pathogens thus allowing for rapid host defense responses to invading microbes. A key component of such receptors is the "Toll-like receptors" (TLRs), which have come to occupy the center stage in innate immunity against invading pathogens. An increasing number of studies have shown that TLRs are expressed by a variety of tissues and cells of the eye and play an important role in ocular defense against microbial infection. Here in this review we summarize the current knowledge about TLR expression in human eye with main emphasis on the cornea, and discuss the future directions of the field.     

Host responses from innate to adaptive immunity after vaccination: Molecular and cellular events

The availability of effective vaccines has had the most profound positive effect on improving the quality of public health by preventing infectious diseases. Despite many successful vaccines, there are still old and new emerging pathogens against which there is no vaccine available. A better understanding of how vaccines work for providing protection will help to improve current vaccines as well as to develop effective vaccines against pathogens for which we do not have a proper means to control. Recent studies have focused on innate immunity as the first line of host defense and its role in inducing adaptive immunity; such studies have been an intense area of research, which will reveal the immunological mechanisms how vaccines work for protection. Toll-like receptors (TLRs), a family of receptors for pathogen-associated molecular patterns on cells of the innate immune system, play a critical role in detecting and responding to microbial infections. Importantly, the innate immune system modulates the quantity and quality of longterm T and B cell memory and protective immune responses to pathogens. Limited studies suggest that vaccines which mimic natural infection and/or the structure of pathogens seem to be effective in inducing long-term protective immunity. A better understanding of the similarities and differences of the molecular and cellular events in host responses to vaccination and pathogen infection would enable the rationale for design of novel preventive measures against many challenging pathogens.     

DEAD-box RNA解旋酶家族在天然免疫应答信号通路中的作用

病毒入侵宿主细胞时,宿主细胞启动抑制病毒复制的免疫机制.同样,病毒也会利用多种手段去逃避先天免疫感应机制的监测以及宿主细胞对外来者的降解,同时还会操纵宿主细胞为自身的增殖提供便利.DEAD-box解旋酶家族是一类存在于宿主细胞中的功能蛋白,它们在转录、剪接、mRNA的合成和翻译等多种细胞过程中起着关键作用.该家族成员拥...     

肠道病毒调控固有免疫的分子机制研究进展

肠道病毒属于小核糖核酸病毒科,包括脊髓灰质炎病毒等多种重要人类病原体,已成为全球公共卫生安全的重大威胁之一。固有免疫是机体早期抵御病毒感染的重要防线。不同肠道病毒在进化中已经具备了多种途径躲避免疫识别或诱导固有免疫系统失活。本文重点对肠道病毒调控宿主固有免疫的相关分子机制进行综述,系统整理了肠道病毒逃避干扰素依赖与干扰素非依赖的抗病毒固有免疫防御的分子特征与作用规律,为肠道病毒致病机制的探究和抗病毒药物的研发提供参考。     

Co-evolution and exploitation of host cell signaling pathways by bacterial pathogens

Bacterial pathogens have evolved by combinations of gene acquisition, deletion, and modification, which increases their fitness. Additionally, bacteria are able to evolve in "quantum leaps" via the ability to promiscuously acquire new genes. Many bacterial pathogens - especially Gram-negative enteric pathogens - have evolved mechanisms by which to subvert signal transduction pathways of eukaryotic cells by expressing genes that mimic or regulate host protein factors involved in a variety of signaling cascades. This results in the ability to cause diseases ranging from tumor formation in plants to gastroenteritis and bubonic plague. Here, we present recent advances on mechanisms of bacterial pathogen evolution, including specific signaling cascades targeted by their virulence genes with an emphasis on the ubiquitin modification system, Rho GTPase regulators, cytoskeletal modulators, and host innate immunity. We also comment briefly on evolution of host defense mechanisms in place that limit disease caused by bacterial pathogens.     

植物与病原微生物互作分子基础的研究进展

植物在与病原微生物共同进化过程中形成了复杂的免疫防卫体系。植物的先天免疫系统可大致分为两个层面。第一个层面的免疫基于细胞表面的模式识别受体对病原物相关分子模式的识别,该免疫过程被称为病原物相关分子模式触发的免疫(PAMP-triggered immunity,PTI),能帮助植物抵抗大部分病原微生物;第二个层面的免疫起始于细胞内部,主要依靠抗病基因编码的蛋白产物直接或间接识别病原微生物分泌的效应子并且激发防卫反应,来抵抗那些能够利用效应子抑制第一层面免疫的病原微生物,这一过程被称为效应子触发的免疫(Effector-triggered immunity,ETI)。这两个层面的免疫都是基于植物对"自我"及"非我"的识别,依靠MAPK级联等信号网络,将识别结果传递到细胞核内,调控相应基因的表达,做出适当的免疫应答。本文着重阐述了植物与病原微生物互作过程中不同层面的免疫反应所发生主要事件的分子基础及研究进展。     

Immunity against extracellular pathogens

Summary Eukaryotic cells live in a relatively comfortable equilibrium with a wide variety of microbes. However, while many of the cohabiting microorganisms are harmless or even beneficial to the eukaryotic host, a number of prokaryotes have evolved the capacity to invade and replicate within host cells, thereby becoming potentially pathogenic. To be able to cope with potential pathogens, most organisms have developed several host defense mechanisms. First, microbes can be internalized and destroyed by a number of cell types of an innate immune system in a rather aspecific manner. Second, more complex organisms possess additionally an adaptive immune system that is capable of eliminating hazardous microbes in a highly specific manner. This review describes recent progress in our understanding of how pathogens interact with cells of the immune system, resulting in activation of the immune system or, for certain microorganisms, in the evasion of host defense reactions.     

Innate immunity and adjuvants

Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection.     

Toll-like receptor 9, CpG DNA and innate immunity

Innate immunity provides the first line of defense against invading pathogens and is essential for survival in the absence of adaptive immune responses. Innate immune recognition relies on a limited number of germ-line encoded receptors, such as Toll-like receptors (TLRs), that evolved to recognize conserved molecular patterns of microbial origin. To date, ten transmembrane proteins in the TLR family have been described. It is becoming increasingly clear that bacterial CpG DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG are potent inducers of the innate immune system including dendritic cells (DCs), macrophages, and natural killer (NK) and NKT cells. Recent studies indicate that mucosal or systemic delivery of CpG DNA can act as a potent adjuvant in a vaccine combination or act alone as an anti-microbial agent. Recently, it was shown that TLR9 is essential for the recognition of unmethylated CpG DNA since cells from TLR9-deficient mice are unresponsive to CpG stimulation. Although the effects of CpG DNA on bone marrow-derived cells are beginning to unfold, there has been little or no information regarding the mechanisms of CpG DNA function on non-immune cells or tissues. This review focuses on the recent advances in CpG-DNA/TLR9 signaling effects on the activation of innate immunity.     

The fifth dimension of innate immunity

Innate immunity has evolved as a first line defense against invading pathogens. Cellular and humoral elements of the innate immune system detect infectious parasites, initiate inflammatory resistance reactions and finally contribute to the elimination of the invaders. Repeated attacks by pathogenic agents induce adaptive responses of the innate immune system. Typically, reapplication of pathogens provokes tolerance of the affected organism. However, also stimulatory effects of primary infections on subsequent innate immune responses have been observed. The present overview touches an undervalued aspect in the innate immune response: Its pronounced dependency on pathogen load. In addition to localization and timing of innate immune responses the pathogen dose dependency might be considered as a “fifth dimension of innate immunity”. Experimental results and literature data are presented proposing a hormetic reaction pattern of innate immune cells depending on the dose of pathogens.     

Plant systems for recognition of pathogen-associated molecular patterns

Research of the last decade has revealed that plant immunity consists of different layers of defense that have evolved by the co-evolutional battle of plants with its pathogens. Particular light has been shed on PAMP- (pathogen-associated molecular pattern) triggered immunity (PTI) mediated by pattern recognition receptors. Striking similarities exist between the plant and animal innate immune system that point for a common optimized mechanism that has evolved independently in both kingdoms. Pattern recognition receptors (PRRs) from both kingdoms consist of leucine-rich repeat receptor complexes that allow recognition of invading pathogens at the cell surface. In plants, PRRs like FLS2 and EFR are controlled by a co-receptor SERK3/BAK1, also a leucine-rich repeat receptor that dimerizes with the PRRs to support their function. Pathogens can inject effector proteins into the plant cells to suppress the immune responses initiated after perception of PAMPs by PRRs via inhibition or degradation of the receptors. Plants have acquired the ability to recognize the presence of some of these effector proteins which leads to a quick and hypersensitive response to arrest and terminate pathogen growth.     

秀丽隐杆线虫固有免疫功能神经调控机制研究进展

固有免疫系统是动植物个体应对外来微生物侵入感染时非常重要的抵御防线。秀丽隐杆线虫(Caenorhabditis elegans,简称线虫)作为研究宿主与病原菌之间相互作用的经典模式动物,近年来在神经和免疫之间相互作用的分子与遗传机制等方面的研究取得了长足进展。研究表明,线虫神经元通过释放神经递质与神经多肽(如多巴胺、NLP-20)等,激活相关信号通路途经,参与线虫对病原菌的识别、逃避、调节物理屏障防御能力和激活固有免疫反应,并表达分泌抗菌肽以清除病原菌等的调控进程。本文综述了线虫神经系统调控固有免疫功能机制的最新研究进展,为人们深入了解神经与免疫系统间相互作用的功能分子及其调控机制和揭示人类神经与免疫系统相关疾病的病理机理提供了重要信息。     

肠粘膜上皮细胞在天然免疫中的作用

粘膜免疫是机体防御系统的主要成分。致病性细菌侵入机体后,首先遭遇到天然免疫的抵抗,随后产生获得性免疫,两共同执行机体的防御功能,消灭入侵细菌。最近的研究表明上皮细胞对细菌感染有重要的免疫调节作用,在天然免疫与获得性免疫防御机制中起重要作用。本重点介绍肠上皮细胞在天然免疫中的作用。     

植物核质运输与其先天免疫研究进展

植物为了抵御病原菌的侵染而进化出一套独特的先天免疫系统,它主要通过定位在细胞膜或细胞质上的受体介导并激活下游抗病基因表达而实现,但在这些信号传递过程中,细胞质的信号向核传递需要核质运输相关元件的参与。虽然目前只有个别核质运输的信号元件被证实参与了植物的先天免疫信号传递过程,但越来越多的研究表明核质运输是连接抗病基因表达和信号识别受体的一个主要方式。研究发现,病原菌的效应因子也可以利用植物核质运输机制侵入到宿主细胞核内,调控敏感基因的表达,干扰植物的免疫反应。该文对近年来国内外有关植物的核质运输机制、各层次免疫反应需要核质运输作用、核质运输相关蛋白在免疫反应中的作用等方面对核质运输参与植物先天免疫反应研究的研究进展进行综述,并指出该领域未来研究的主要内容和方向。     

Innate recognition of malarial parasites by mammalian hosts

Innate immunity plays a central role in combating infections. However, the importance of innate immune sensors in detecting intracellular parasites, such as Plasmodium spp., has only recently emerged as a central topic in the field of host-pathogen interactions. Genetic dissection of innate immune pathways has uncovered a complex relationship between the host innate immune system and Plasmodium blood-stage parasites. In fact, recognition molecules of the innate immune system, such as toll-like receptors, might not only be implicated in host defense but also in the pathogenesis of the disease. Whether Plasmodium liver stage parasites are recognised and controlled by the host innate immune system remains to be discovered. In this review we discuss recent findings on how the host innate immune system may sense and fight the different forms of Plasmodium and how the latter may have evolved mechanisms to escape host detection and/or to manipulate the defensive reaction of the host.