Toll-like receptors and innate immunity

The innate immune system is an evolutionally conserved host defense mechanism against pathogens. Innate immune responses are initiated by pattern recognition receptors (PRRs), which recognize specific structures of microorganisms. Among them, Toll-like receptors (TLRs) are capable of sensing organisms ranging from bacteria to fungi, protozoa, and viruses, and play a major role in innate immunity. However, TLRs recognize pathogens either on the cell surface or in the lysosome/endosome compartment. Recently, cytoplasmic PRRs have been identified to detect pathogens that have invaded cytosols. In this review, we focus on the functions of PRRs in innate immunity and their downstream signaling cascades.     

Toll-like receptors and their crosstalk with other innate receptors in infection and immunity

Toll-like receptors (TLRs) are germline-encoded pattern recognition receptors (PRRs) that play a central role in host cell recognition and responses to microbial pathogens. TLR-mediated recognition of components derived from a wide range of pathogens and their role in the subsequent initiation of innate immune responses is widely accepted; however, the recent discovery of non-TLR PRRs, such as C-type lectin receptors, NOD-like receptors, and RIG-I-like receptors, suggests that many aspects of innate immunity are more sophisticated and complex. In this review, we will focus on the role played by TLRs in mounting protective?immune responses against infection and their crosstalk with other PRRs with respect to pathogen recognition.     

Role of DC-SIGN and L-SIGN receptors in HIV-1 vertical transmission

The innate immune system acts in the first line of host defense against pathogens. One of the mechanisms used involves the early recognition and uptake of microbes by host professional phagocytes, through pattern recognition receptors (PRRs). These PRRs bind to conserved microbial ligands expressed by pathogens and initiate both innate and adaptative immune responses. Some PRRs located on the surface of dendritic cells (DCs) and other cells seem to play an important role in human immunodeficiency virus type 1 (HIV-1) transmission. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin, CD209 (DC-SIGN) and its homolog, DC-SIGN-related (DC-SIGNR or L-SIGN) receptors are PPRs able to bind the HIV-1 gp120 envelope protein and, because alterations in their expression patterns also occur, they might play a role in both horizontal and vertical transmission as well as in disseminating the virus within the host. This review aims to explore the involvement of the DC-SIGN and L-SIGN receptors in HIV-1 transmission from mother to child.     

Antiviral Signaling Through Retinoic Acid-Inducible Gene-I-Like Receptors

The innate immune system is essential for the first line of host defense against micropathogens. In virus-infected cells, exposed viral nucleotides are sensed by pattern recognition receptors (PRRs), resulting in the induction of type I interferon. Retinoic acid-inducible gene-I-like receptors (RLRs) are a member of PRRs and are known to be crucial molecules in innate immune responses. Upon viral recognition, RLRs recruit their specific adaptor molecules, leading to the activation of antiviral signaling molecules including interferon regulatory factor-3 and nuclear factor-κB. Mitochondrial antiviral signaling (MAVS) protein is also known as one of the adaptor molecules responsible for antiviral signaling triggered by RLRs. Recent reports have identified numerous intracellular molecules involved in the antiviral responses mediated by RLRs/MAVS. Several viral proteins interfere with the RLR/MAVS signaling, allowing the virus to evade the host defense. In this review, we comprehensively update RLR-dependent antiviral signaling with special reference to the RLRs/MAVS-mediated responses.     

Pattern recognition receptors

Immunity is based on self/nonself discrimination. In vertebrates, two major systems, innate and adaptive immune systems, constitute host defense against invading microbes. Adaptive immunity is characterized by specific immune responses through B- or T-cell antigen receptors that are generated by somatic recombination, whereas nonspecific responses to microbes had been accentuated in innate immunity. However, the discovery of pattern recognition receptors (PRRs) that are encoded in the germ-line, including Toll-like receptors, RIG-I-like receptors, NOD-like receptors and AIM2-like receptors, advanced our understanding of a mechanism for innate immune recognition. These types of PRR recognize pathogen- or damage-associated molecular patterns (PAMPs or DAMPs) during infection or tissue damage, and commonly evoke the downstream gene induction programme, such as expression of type I interferons, inflammatory cytokines and chemokines. Dysregulation of PRR-triggered signal activation leads to pathologic inflammatory responses. In this regard, it has been shown that many of "autoinflammatory diseases", recently defined clinical entity, have putatively causative mutations in the genes that encode PRRs or their signaling mediators. In this review article, we describe recent overview of PRRs as innate sensors and update knowledge of "autoinflammatory diseases" particularly by focusing on their association with innate signaling.     

Pattern recognition receptors for respiratory syncytial virus infection and design of vaccines

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants and young children. Host immune response has been implicated in both the protection and immunopathological mechanisms. Pattern recognition receptors (PRRs) expressed on innate immune cells during RSV infection recognize the RSV-associated molecular patterns and activate innate immune cells as well as mediate airway inflammation, protective immune response, and pulmonary immunopathology. The resident and recruited innate immune cells play important roles in the protection and pathogenesis of an RSV disease by expressing these PRRs. Agonist-binding PRRs are the basis of many adjuvants that are essential for most vaccines. In the present review, we highlight recent advances in the innate immune recognition of and responses to RSV through PRRs, including toll-like receptors (TLRs), retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). We also describe the role of PRRs in the design of RSV vaccines.     

Pathogen Recognition by the Innate Immune System

Microbial infection initiates complex interactions between the pathogen and the host. Pathogens express several signature molecules, known as pathogen-associated molecular patterns (PAMPs), which are essential for survival and pathogenicity. PAMPs are sensed by evolutionarily conserved, germline-encoded host sensors known as pathogen recognition receptors (PRRs). Recognition of PAMPs by PRRs rapidly triggers an array of anti-microbial immune responses through the induction of various inflammatory cytokines, chemokines and type I interferons. These responses also initiate the development of pathogen-specific, long-lasting adaptive immunity through B and T lymphocytes. Several families of PRRs, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and DNA receptors (cytosolic sensors for DNA), are known to play a crucial role in host defense. In this review, we comprehensively review the recent progress in the field of PAMP recognition by PRRs and the signaling pathways activated by PRRs.     

Pathogen recognition by the innate immune system

Microbial infection initiates complex interactions between the pathogen and the host. Pathogens express several signature molecules, known as pathogen-associated molecular patterns (PAMPs), which are essential for survival and pathogenicity. PAMPs are sensed by evolutionarily conserved, germline-encoded host sensors known as pathogen recognition receptors (PRRs). Recognition of PAMPs by PRRs rapidly triggers an array of anti-microbial immune responses through the induction of various inflammatory cytokines, chemokines and type I interferons. These responses also initiate the development of pathogen-specific, long-lasting adaptive immunity through B and T lymphocytes. Several families of PRRs, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), and DNA receptors (cytosolic sensors for DNA), are known to play a crucial role in host defense. In this review, we comprehensively review the recent progress in the field of PAMP recognition by PRRs and the signaling pathways activated by PRRs.     

The role of Toll-like receptors and Nod proteins in bacterial infection

Our understanding of innate immunity in mammals has greatly expanded following the discovery of the family of membrane-bound receptors, called the Toll-like receptors (TLRs). More recently, the nucleotide-binding oligomerisation domain (Nod) molecules, Nod1 and Nod2, which are cytoplasmic surveillance proteins, have also been shown to be involved in the innate immune response. These two classes of detection molecules, classified as "pattern recognition receptors" (PRRs), detect microbial ligands in order to initiate a defense response to fight infectious disease. These microbial ligands or "pathogen-associated molecular patterns" (PAMPs), detected by TLRs and Nods are often structural components of the microorganism that are not subject to much variation. These include such factors as lipopolysaccharide (LPS) and peptidoglycan from the cell walls of bacteria. In order to understand the role of TLRs and Nod proteins in infectious disease in vivo it is important to define the site of interaction between PRRs and PAMPS. Additionally, the challenge of mice deficient in the various PRRs in natural infection models will help to decipher the contribution of these molecules not only in the innate immune response against pathogen infection but also how these proteins may instruct the adaptive immune response in order to have a tailored immune response against a particular microbe.     

Innate signaling and regulation of Dendritic cell immunity

Dendritic cells are crucial in pathogen recognition and induction of specific immune responses to eliminate pathogens from the infected host. Host recognition of invading microorganisms relies on evolutionarily conserved, germline-encoded pattern-recognition receptors (PRRs) that are expressed by DCs. The best-characterized PRR family comprises the Toll-like receptors (TLRs) that recognize bacteria or viruses. In addition to TLRs, intracellular Nod-like receptors and the membrane-associated C-type lectins (CLRs) function as PRRs. Many of these innate receptors also have an important function in natural host homeostatic responses, such as the maintenance of gut homeostasis. Clearly, more indications are hinting at a fine-tuning of immune responses by a concerted action of these PRRs on the recognition of pathogen components and the consequent signalling events that are created. It is becoming increasingly clear that these PRRs can initiate specific signalling events that modulate the production of inflammatory cytokines, phagocytosis, intracellular routing of antigen, release of oxidative species and DC maturation and the subsequent development of adaptive immunity. Notably, members within one family of PRRs can trigger opposite signalling features, indicating that the ultimate outcome of pathogen-induced immune responses depends on the pathogen signature and the collective PRRs involved.     

Intracellular Roles of Microbial Aminotransferases: Overlap Enzymes Across Different Biochemical Pathways

Microbial challenges to the host initiate an array of defense processes through the activation of innate and adaptive immunity. Innate immunity consists of sensors or pattern-recognition receptors (PRRs) that are expressed on immune and non-immune cells and sense conserved pathogen-derived molecules or pathogen-associated molecular patterns (PAMPs) in various compartments of the host cells. Recognition of the PAMPs by PRRs triggers antimicrobial effector responses via the induction of proinflammatory cytokines and type I IFNs. Several families of PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and DNA sensors and their respective PAMPs have been well studied in innate immunity and host defense. Here, we review the recent findings on bacterial recognition by TLRs and NLRs and the signaling pathways activated by these sensors.     

Age-related macular degeneration: activation of innate immunity system via pattern recognition receptors

Age-related macular degeneration (AMD) is the most common cause of irreversible loss of central vision. Histopathological studies have demonstrated that inflammation is the key player in the pathogenesis of AMD. Genetic studies have revealed that complement factor H is a strong risk factor for the development of AMD. However, innate immunity defence involves several other pattern recognition receptors (PRRs) which can trigger inflammatory responses. Retinal pigment epithelial (RPE) cells have the main role in the immune defence in macula. In this study, we examine in detail the endogenous danger signals which can activate different PRRs in RPE cells, such as Toll-like, NOD-like and scavenger receptors along with complement system. We also characterise the signalling pathways triggered by PRRs in evoking inflammatory responses. In addition, we will discuss whether AMD pathology could represent the outcome of chronic activation of the innate immunity defence in human macula.     

Innate immunity related pathogen recognition receptors and chronic hepatitis B infection

Innate immunity consists of several kinds of pathogen recognition receptors (PRRs), which participate in the recognition of pathogens and consequently activation of innate immune system against pathogens. Recently, several investigations reported that PRRs may also play key roles in the induction/stimulation of immune system related complications in microbial infections. Hepatitis B virus (HBV), as the main cause of viral hepatitis in human, can induce several clinical forms of hepatitis B and also might be associated with hepatic complications such as cirrhosis and hepatocellular carcinoma (HCC). Based on the important roles of PRRs in the eradication of microbial infections including viral infections and their related complications, it appears that the molecules may be a main part of immune responses against viral infections including HBV and participate in the HBV related complications. Thus, this review article has brought together information regarding the roles of PRRs in immunity against HBV and its complications.     

Pattern recognition receptors and coordinated cellular pathways involved in tuberculosis immunopathogenesis: Emerging concepts and perspectives

Pattern Recognition Receptors (PRRs) play a central role in the recognition of numerous pathogens, including Mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. Besides Toll Like Receptors, C-type Lectin Receptors and Nod Like Receptors are now being recognized for their involvement in inducing immune response against M. tuberculosis infection. Although, a functional redundancy of the PRRs has also been reported in many studies, emerging evidences support the notion that a cooperative and coordinated response generated by these receptors is critical to sustain the full immune control of M. tuberculosis infection. Many of the PRRs are now found to be involved in various cellular host defenses, such as inflammasome activation, phagosome biogenesis, endosomal trafficking, and antigen processing pathways that are all very critical for an effective immune response against M. tuberculosis. In support, polymorphism in several of these receptors has also been found associated with increased susceptibility to tuberculosis in humans. Nonetheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to subvert and reprogram PPR-mediated immune responses. In light of these findings, this review analyzes the interaction of bacterial and host factors at the intersections of PRR signaling pathways that could provide integrative insights for the development of better vaccines and therapeutics for tuberculosis.     

NOD1,NOD2和NLRP3炎症小体与牙髓炎

模式识别受体(pattern recognition receptors,PRRs)识别病原相关分子模式(pathogen associated molecule patterns,PAMP)激活固有免疫系统,是抵抗病原微生物入侵的第一道防线.核苷酸结合寡聚化结构域蛋白(nucleotide-binding oligomerization domains,NODs)和NOD样受体蛋白3(NODlike protein 3,NLRP3)属胞质内PRRs家族.NOD1和NOD2激活NF-κB,MAPK,JNK,p38和ERK信号通路,促进TNF-α,IL-1β,IL-6,IL-8和IL-12等多种炎性因子的转录表达.NLRP3炎症小体激活caspase-1,并促进IL-18和IL-1β表达.牙髓位于低顺应性根管系统中,牙髓环境环境与机体其他组织不同.目前的研究表明NOD1,NOD2和NLRP3炎症小体与牙髓固有免疫及牙髓炎的发生、发展有关.     

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.     

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。     

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.