Biological Sciences
Pattern Recognition Receptors
Pattern recognition receptors (PRRs) are a crucial component of the innate immune system, responsible for detecting and responding to various pathogens and danger signals. They recognize specific molecular patterns, such as those found on the surface of bacteria, viruses, and fungi, and initiate immune responses to combat these threats. PRRs play a fundamental role in the body's defense against infections and maintaining homeostasis.
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12 Key excerpts on "Pattern Recognition Receptors"
eBook - PDF- Deniz Ekinci(Author)
- 2012(Publication Date)
- IntechOpen(Publisher)
The 2011 Noble Prize for Medicine was awarded to three scientists who have done more than anyone to lay bare the two-tier structure of the immune system. One area of particular interest is the discovery of agonists that target the PRRs. Adaptive immune responses are essential for the control of pathogens that escape elimination by the innate immune response(Schwartz 2000). Because of its role in immune memory, the adaptive immune systems contributions to pathogen elimination and vaccine development have been widely studied. Adaptive immunity mediates a delayed, specific response to foreign antigen while innate immunity is not antigen specific and develops immediately following exposure to immune stimuli i.e., pathogens. 4. Pattern Recognition Receptors The Pattern Recognition Receptors (PRRs) of the innate immune system serve an essential role in recognition of pathogen and directing the course as well as type of innate immune response generated following exposure to foreign antigen. PRRs are differentially expressed on a wide variety of immune cells(Iwasaki and Medzhitov 2004). Engagement of PRRs invokes the cascades of intracellular signaling events that further induce many processes such as activation, maturation and migration of other immune cells and the secretion of cytokines and chemokines(Hoebe, Janssen et al. 2004; Medzhitov 2007; Kumar, Kawai et al. Pattern Recognition Receptors Based Immune Adjuvants: Their Role and Importance in Vaccine Design 179 2009; Blasius and Beutler 2010; Kawai and Akira 2010; Takeuchi and Akira 2010). This creates an inflammatory environment in tandem, that leads to the establishment of the adaptive immune response(Iwasaki and Medzhitov 2004). PRRs consist of non-phagocytic receptors such as toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) proteins and receptors that induce phagocytosis such as scavanger receptors , mannose receptors and β -glucan receptors .
eBook - PDFAstrocytes
Wiring the Brain
- Eliana Scemes, David C. Spray(Authors)
- 2016(Publication Date)
- CRC Press(Publisher)
4.3 Pattern Recognition Receptors (PRRs) Numerous CNS resident cell types express Pattern Recognition Receptors (PRRs), which recognize pathogen-associated molecular patterns (PAMPs), revealing the ability of the CNS to initiate a local immune response to infectious insults (Kielian 2006). Besides PAMPs, some PRRs can also recognize endogenous stress-related or degradation molecules termed danger-associated molecular patterns (DAMPs), which are elaborated following brain insults other than infections, such as ischemia and neurodegenerative disorders (Bianchi 2007; Carta et al. 2009). Currently, PRRs can be classified into three groups: membrane bound, cytosolic, or secreted (Box 4.1). The variety of PRRs and their expression in both immune-competent as well as nonimmune CNS cell types support the concept that their relevance extends far beyond a role in antimicrobial defense. Among the PRRs, Toll-like receptors (TLRs) form the largest and most diverse group in terms of their ability to recognize a broad spectrum of PAMPs (Takeda et al. 2003; Medzhitov 2001; van Noort and Bsibsi 2009). Since their discovery, we continue to acquire new information about TLR ligands, their locations, mechanisms of activation, and signaling outcomes. For example, TLR2, which has the largest ligand repertoire of all TLR family members identified to date, has recently been documented to be important for the recognition of viral proteins (Barbalat et al. 2009; Martinez et al. 2010). In addition, TLR4, which is the only TLR capable of inducing both MyD88-dependent and -independent signaling pathways following activation by Gram-negative bacteria, has been recently shown to translocate into an endosomal compartment upon ligation and MyD88-dependent activation, where it induces MyD88-independent, i.e., TRIF-related adaptor molecule (TRAM)-TIR domain-containing adapter-inducing interferon-beta (TRIF) signaling (Kagan et al. 2008).
eBook - ePub- Dhia Bouktila, Yosra Habachi(Authors)
- 2021(Publication Date)
- Bentham Science Publishers(Publisher)
paradigm change in the plant defense field and instigated the recognition of PTI as a critically important component of the plant defense machinery. Since then, several new PRR candidate genes have been identified.1. PATTERN-RECOGNITION RECEPTORS (PRRs)
1.1. An Overview: Nature of PAMPs and Biochemical Structure of PRRs
Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) to microbial infection constitutes an evolutionarily ancient type of immunity that is characteristic of all multicellular eukaryotic living things. Microbial patterns (PAMPs) activating plant PTI have been conserved through evolution ; in other words, these are molecules present in microorganisms, and which are slowly evolving due to the critical functions they exert for survival. These molecules, which are detected by PRRs, are diverse: bacterial (flagellin, elongation factor EF-Tu, and peptidoglycan) (), fungal (chitin, xylanase) (Gust et al. 2007), oomycete (β-glucan and elicitins) (Kaku et al. 2006), viral (double stranded RNA) (Du et al. 2015), and insect (aphid-derived elicitors) (Niehl et al. 2016).Prince et al. 2014Plant Pattern-Recognition Receptors (PRRs) mediate microbial pattern sensing and subsequent immune activation. PRRs include a range of non-specific receptors. These receptors often possess leucine-rich repeats (LRRs) that bind to extracellular ligands, transmembrane domains necessary for their localization in the plasma membrane, and cytoplasmic kinase domains for signal transduction through phosphorylation (Zipfel 2014 ). LRRs are highly divergent, associated with their ability to bind to diverse elicitors. Numerous PRRs rely on the regulatory protein brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) and other somatic embryogenesis receptor-like kinases (SERKs) ()2 .Prince et al. 20141.2. Best Known Examples of Bacterial and Fungal PAMPs and their Cognate Pattern Recognition Receptors
The LRR-RLKs FLS2, EFR and Xa21 are capable of detecting bacterial peptides such as flg22 from flagellin, elf18 from EF-Tu and AxYs22 from Ax21, respectively (;Kaku et al. 2006Gust et al
eBook - PDF- A. Egesten, A. Schmidt, H. Herwald, A. Schmidt, H. Herwald(Authors)
- 2008(Publication Date)
- S. Karger(Publisher)
Egesten A, Schmidt A, Herwald H (eds): Trends in Innate Immunity. Contrib Microbiol. Basel, Karger, 2008, vol 15, pp 45–60 Pattern Recognition Receptors and Their Role in Innate Immunity: Focus on Microbial Protein Ligands Thomas Areschoug a Siamon Gordon b a Department of Laboratory Medicine, Division of Medical Microbiology, Lund University, Lund, Sweden; b Sir William Dunn School of Pathology, University of Oxford, Oxford, UK Abstract Antigen-presenting cells, such as macrophages and dendritic cells, represent a central and important part of the immune defence against invading microorganisms, as they participate in initial capture and process-ing of microbial antigens (innate immunity) and then activation of specific T and B cell effector mechanisms (acquired immunity). Recognition of microbial molecules by antigen-presenting cells occurs through so called Pattern Recognition Receptors (PRRs), which recognize conserved structures, or pathogen-associated molecular patterns, in pathogenic microbes. The Toll-like receptors are the most extensively studied of these receptors, but accumulating evidence shows that other PRRs, such as scavenger receptors, C-type lectin receptors and NOD-like receptors, also play important roles in the innate immune defence. Here, we summarize current knowledge of the role of various PRRs in the defence against pathogenic microorgan-isms and we report recent advances in studies of different receptor-ligand interactions. In particular, we focus on the importance of microbial proteins as ligands for PRRs. Copyright © 2008 S. Karger AG, Basel Antigen-presenting cells (APCs), i.e. macrophages and dendritic cells, are widely dis-tributed in the body, including at sites of possible entry for pathogenic microorgan-isms.
eBook - PDFProbiotics
Immunobiotics and Immunogenics
- Haruki Kitazawa, Julio Villena, Susana Alvarez(Authors)
- 2013(Publication Date)
- CRC Press(Publisher)
A wide range of bacteria share conserved pathogen-derived molecules, pathogen-associated molecular patterns (PAMPs) or microbe-associated molecular patterns (MAMPs) (Akira and Hemmi 2003; Mackey and McFall 2006). In the innate immune system, these molecules interact with PRRs expressed on immune and non-immune cells (Table 1) (Gordon 2002; Kawai and Akira 2007; Akira 2009; Kawai and Akira 2010; Takeuchi and Akira 2010; Kumar et al. 2011). When PRRs recognize PAMPs, various anti-microbial immune responses are triggered through the induction of various inflammatory cytokines, inflammatory enzymes, chemokines, type I interferons and anti-microbial peptides (Kumar et al. 2012). These innate immune responses also induce the development of pathogen-specific, long-lasting adaptive immune responses through the involvement of B and T lymphocytes (Akira et al. 2001; Pasare and Medzhitov 2004). Therefore, the innate immune system constitutes the first line of recognition of many microorganisms, and is essential for the control of bacterial invasion. Several families of PRRs, such as toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-1)-like receptors (RLRs), and cytosolic DNA receptors [(DNA-dependent activator of interferon-regulatory factors (DAI)] play an important role in host defense (Martinon and Tschopp 2005; Takaoka et al. 2007; Kawai and Akira 2008; Ting et al. 2008; Wang et al. 2008; Kumar et al. 2011; Kumar et al. 2012). In the TLR family (Fig. 1), TLR2, together with TLR1 and TLR6, recognize a wide variety of PAMPs, such as peptidoglycan, lipopeptides and lipoproteins of Gram-positive bacteria, mycoplasma lipopeptides and fungal zymosan (Jin et al. 2007). TLR4/myeloid differentiation protein (MD)-2 and radio protective MW105 (RP105)/ MD-1 are involved in the detection of lipopolysaccharide (LPS) from gram-negative bacteria (Miyake et al. 1995; Poltorak et al. 1998).
eBook - ePubThe Innate Immune System
A Compositional and Functional Perspective
- Tom Monie(Author)
- 2017(Publication Date)
- Academic Press(Publisher)
2.2.5. Cytoplasmic Pattern Recognition Receptors
It might be fair to say that the presence of PAMPs, DAMPs, or damage in the cytoplasm presents a potentially higher risk to the host, or at least the individual cell, than those that are extracellular or have been internalized as a result of pathogen/danger-mediated endocytosis. Consequently, it should be of no surprise that there are a diverse range of intracellular PRRs, whose role is to rapidly detect and respond to intracellular threats. As our understanding of the mechanisms involved in the cytoplasmic detection of cellular danger continues to improve, the repertoire of proteins and receptors involved in these pathways continues to expand. At the broadest level, these receptors can be broken down into two categories, those that detect nucleic acids, and those that do not. It is, however, more common to consider these receptors in the context of their actual signaling families, which is what shall be done here.2.2.6. Nucleotide-Binding, Leucine-Rich Repeat-Containing Receptor Signaling
The NLR family are tripartite proteins that contain an N-terminal effector domain, a central NACHT domain within which is contained a nucleotide-binding domain, and a C-terminal leucine-rich repeat (Fig. 2.5 ). This domain organization shares strong parallels with the Resistance, or R proteins, which play a central role in the innate defenses of plants against pathogens. The NLRs are split into subfamilies based upon the identity of their N-terminal effector domains. The key subfamilies are the NLR family member with a CARD (NLRC) and NLR family member with a pyrin (NLRP).A selection of the NLRs—NOD1, NOD2, NAIP, NLRC4, NLRP1, NLRP3—function as bona fide PRRs and activate an inflammatory immune response following detection of their activatory ligands. Others, such as NLRC5 and NLRP12, are also suggested to have PRR-related roles in the detection of viral and bacterial infections, respectively. NLRP6 is a crucial mediator of intestinal homeostasis and the maintenance of intestinal immunity. Commensal bacteria, especially segmented filamentous bacteria, are important for this functionality, but the exact mechanisms involved remain to be elucidated. NLRs also have a role to play in the transcriptional regulation of the MHC genes required for activation of the adaptive immune response. NLRC5 and CIITA control the expression of class I and class II MHC, respectively (see Section 5 ). NLRC3 negatively regulates inflammatory signaling through TLRs and STING, and NLRP4 has been associated with regulating autophagy. In a manner analogous to the Toll protein family in Drosophila melanogaster , a number of the NLRP genes appear to have roles in development, and polymorphisms in NLRP7
eBook - ePubImmunology
Mucosal and Body Surface Defences
- Andrew E. Williams(Author)
- 2011(Publication Date)
- Wiley(Publisher)
They were first discovered in the fruit fly Drosophilia melanogaster ; the original toll gene being initially implicated in development and later in immunity against certain fungi. Homologues were soon discovered in mammals, of which there are a total of 13 that have so far been identified, 10 recognized in humans and 12 in mice, of which TLR1-9 are conserved between the two species. These TLRs are all encoded by the germline and are known as Pattern Recognition Receptors (PRRs). Each TLR specifically recognizes one type of microbial component, or pathogen associated molecular pattern (PAMP), such as lipopolysaccharide (LPS), lipopeptides, RNA or DNA. The expression of several different TLRs enables a number of different PAMPs to be recognized (Figure 2.3), allowing the detection of viruses, bacteria, fungi and protozoa. Therefore, TLRs are often expressed by cells at the front line of immune defence, such as epithelial cells and DCs, so that a response to infection can immediately be initiated. Figure 2.3 Recognition of PAMPs by TLRs. Several TLRs are expressed on the cell surface and recognise a diverse array of PAMPs contained in the extracellular environment. Other TLRs are expressed on the membranes of endosomes and recognize PAMPs that have been endocytosed. TLRs also represent an important means of discriminating between one's own molecules and foreign molecules. This enables a distinction between self and non-self, a concept that is often referred to as the danger signal hypothesis. Considering that TLRs only recognize components derived from microbes and not host factors, they provide a danger signal to the immune system when a pathogen enters the body
- Jane Parker(Author)
- 2009(Publication Date)
- Wiley-Blackwell(Publisher)
This chapter highlights recent progress made in PAMP research, with particular emphasis on the findings mentioned above. Keywords: pathogen-associated molecular pattern; pattern recognition; receptor, immunity; plant defence; effector 2.1 The concept of plant immunity Numerous recent papers addressing diverse aspects of plant defence, disease resistance or susceptibility have adopted a terminology that differs largely 16 PAMP and PAMP-Triggered Immunity 17 from that applied 5 years ago. This development is characterised by the use of such terms as innate immunity, pathogen-associated molecular pat-tern (PAMP), Pattern Recognition Receptors (PRRs), effectors and so on. An immunity-associated terminology has in large parts replaced a more tradi-tional phytopathological vocabulary that dominated the literature for many years. As there is still some confusion among readers in the field, there is a need to address the adequacy of an immunity-associated terminology in describing plant disease resistance. In general, the term ‘immunity’ refers to the state of having sufficient biological defences to avoid infection, dis-ease or other unwanted biological invasion. As this definition applies to all multicellular eukaryotic systems, it is appropriate to describe the ability of plants to cope with microbial infections as an ‘immune’ response. The ques-tion why such a change in vocabulary has occurred only recently is pertinent. Notwithstanding early discussions of analogies between plant disease re-sistance genes and the major histocompatibility complex of animal systems (Dangl, 1992), the driving force for this shift has been the recent re-evaluation of innate immunity in jawed vertebrates as a prerequisite for the contain-ment of microbial infection and for mobilisation of the adaptive immune system.
eBook - PDF- Dr. Prakash Sambhara(Author)
- 2012(Publication Date)
- CRC Press(Publisher)
However, the discoveryofToll as a receptor recognizinginvadingpathogens in the fruit fly Drosophila melanogaster} followed by cloningofmammalian Toll-like receptor,2 revealed that the innate immune system is able to recognize a variety of molecules derived from pathogens, and even to control acquired immunity. Ten and 13 Toll-like receptors (TLRs) have so far been identified in human and mouse, respectively.3 These germ line-encoded receptors can sense a broad range ofcompounds called pathogen-associated molecular patterns (PAMPs), which include proteins, bacterial cell wall components such as sugars and lipids and nucleic acids. After recognition, TLRs induce intracellular signalingcascades that lead to pleiotropic responses, including the production ofproinflammatory cytokines, and consequendy contribute to the activation of the acquired immune response. Mammalian TLR3, TLR7, TLR8 and TLR9 can recognize nucleic acids ofpathogens and elicit pathogen-specific immune responses (Fig. I).3These nucleic acid-sensing TLRs are essential for inducing protective vaccination against viruses. The intracellular signaling cascades downstream of these receptors have been recendy described. In this review, we present the current understanding ♦Laboratory of Host Defense, WPI Immunology Frontier Research Center, and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. Corresponding Author: Yutaro Kumagai— Email: [email protected] Nucleic Acid Sensors and Antiviral Immunity , edited by Suryaprakash Sambhara and Takashi Fujita. ©2013 Landes Bioscience. Nucleic Acid-Sensing TLR Signaling Pathways 41 Figure 1. Nucleic acid-sensing TLRs. Human and mouse TLR3, 7, 8, and 9 recognize nucleic acid ligands. TLR3 recognizes poly(l:C), Semliki Forest virus (SFV), encephalomyocarditis virus (EMCV), and West Nile virus (WNV).
eBook - ePubAllergens and Respiratory Pollutants
The Role of Innate Immunity
- Marc A. Williams(Author)
- 2011(Publication Date)
- Woodhead Publishing(Publisher)
section 12.4.3 .12.4.2.2 Intracellular CLR signaling and gene expression
An important feature of any PRR is not just the ability to recognize specific pathogen-associated molecular patterns but also the capacity to signal downstream to innate immunity genes. Once again dectin-1 is one of the better characterized CLRs in this respect and has been reviewed in detail elsewhere.( 75 ) Briefly, TLR2 was one of the first PRR identified to recognise zymosan,( 69 ) though it appears that dectin-1 may also be important in this respect. Dectin-1 engagement results in signaling through Syk with downstream activation of the mitogen-activated protein kinases p39, Erk and Jnk and NFκB and the activation of innate immune genes.( 63 ) Syk may be an important signaling molecule for several CLRs, either through direct activation or via immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor proteins. The downstream result of these activation pathways generally results in cytokine production such as IL-2, IL-10, IL-12 and TNFα. ( 69 ) DCIR and MICL have also been shown to have an immunoreceptor tyrosine-based inhibitory motif (ITIM), but it is unknown if these ITIM-containing lectins can deliver negative signals to DC.( 76 , 77 )Some CLRs may also modify the responses induced by other receptors. In this regard, BDCA-2 cross-linking on plasmacytoid DC suppresses TLR-induced production of IFNα/β. ( 72 ) DC immunoreceptor (DCIR) can also suppress TLR9-induced IFNα production by plasmacytoid DC while not affecting the upregulation of co-stimulatory molecules.( 78 ) One important aspect of this study was the efficient presentation of antigens targeted through the DCIR to T cells. Similarly, DC-SIGN ligation amplifies the LPS-stimulated IL-10 response mediated by TLR4 while concurrently preventing DC maturation.( 79 , 80 ) Dectin-1 can also synergize with both TLR2 and TLR4 ligands to increase TNFa production.( 81 ) Overall a complex picture is emerging whereby CLRs play an important role in mediating the innate immune response to pathogens either directly or by altering the response of other PRR such as the TLRs. As described below (section 12.4.3
eBook - PDF- Ken J. Ishii, Shizuo Akira, Ken J. Ishii, Shizuo Akira(Authors)
- 2008(Publication Date)
- CRC Press(Publisher)
The first viral pathogen-associated molecular pattern (PAMP) found to induce immune activation was viral double-stranded RNA (dsRNA). 1 After a few reports of similar immune activation by single-stranded RNA (ssRNA) prepa-rations, 2,3 other studies failed to detect such responses in vitro and in vivo , 4,5 and the common belief was that ssRNA did not harbor immunostimulatory activity. 190 Nucleic Acids in Innate Immunity However, these early studies employed ssRNA in the form of naked nucleic acid and rapid degradation by RNases was most likely the reason why no immune activa-tion could be detected. In contrast, viral dsRNA is relatively stable and was found to trigger cytoplasmic PRRs such as double-stranded RNA-dependent protein kinase PKR, 2 ′ 5 ′ -oligoadenylate synthetase, and the recently identified helicases RIG-I and MDA-5. 6–10 All of these cytoplasmic PRRs are ubiquitously expressed and serve as crucial mediators of interferon responses in infected cells. This enabled a detailed characterization of the immunostimulatory activity of dsRNA long before the pat-tern recognition hypothesis was postulated. Only after Janeway’s hypothesis was published in 1989 11 was the search for spe-cialized PRRs incited. The pattern recognition hypothesis postulated that cells of the innate immune system express receptors capable of detecting PAMP without the cells having to be infected with the pathogen, distinguishing these receptors from cytoplasmic PRRs such as RIG-I. The PRRs later found to possess these properties all belonged to a single family: the Toll-like receptor (TLR) family. 12 The TLR mediating detection of viral dsRNA was established to be TLR3. 13 It then became obvious that certain ssRNA viruses such as influenza virus and vesicular stomatitis virus activate the immune system via a TLR-mediated TLR3-independent recognition pathway iden-tified as TLR7.
eBook - PDF- Kenia Pedrosa Nunes(Author)
- 2015(Publication Date)
- IntechOpen(Publisher)
Furthermore, microvascu‐ lar complications in diabetic patients result in considerable morbidity, particularly diabetic nephropathy, retinopathy, and atherosclerosis. A hallmark of diabetic vas‐ cular pathology is inflammation and endothelial dysfunction. Recent literature sug‐ gests that TLR signaling is involved in vascular inflammation and endothelial dysfunction and that TLR activation may play a crucial role in diabetic microangi‐ opathy. However, the mechanisms by which TLRs and their ligands contribute to T1D are not yet clear, and further investigation is needed. The goal of the present chapter is to address the contribution of TLRs to the mechanisms leading to the de‐ velopment and progression of T1D and to review current possibilities of targeting TLRs to forestall diabetic complications. Keywords: Toll-like receptors, type 1 diabetes, DAMPS, innate immune system, microan‐ giopathy © 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction The innate immune system is the first line of defense against invading organisms and other dangerous events in our body. Unlike the acquired immune system, innate immunity identifies the presence of harm via Pattern Recognition Receptors (PRRs). Toll-like receptors (TLRs) are one of the most important classes of PRRs for sensing harmful signals. TLRs can recognize two types of molecules: (1) conserved pathogen molecules such as lipopolysaccharide (LPS), proteins, and nucleic acids expressed by microbes, viruses, bacteria, and fungi, which are known as pathogen-associated molecular patterns or PAMPS [1-2] and (2) endogenous molecules released from damaged cells or tissues such as HMGB-1, HSP60, and C-reactive protein called damage-associated patterns or DAMPS [3].
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