Pattern recognition receptor Dotaz Zobrazit nápovědu
The existence of pattern recognition receptors (PRRs) on immune cells was discussed in 1989 by Charles Janeway, Jr., who proposed a general concept of the ability of PRRs to recognize and bind conserved molecular structures of microorganisms known as pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, PRRs trigger intracellular signaling cascades resulting in the expression of various proinflammatory molecules. These recognition molecules represent an important and efficient innate immunity tool of all organisms. As invertebrates lack the instruments of the adaptive immune system, based on "true" lymphocytes and functional antibodies, the importance of PRRs are even more fundamental. In the present review, the structure, specificity, and expression profiles of PRRs characterized in annelids are discussed, and their role in innate defense is suggested.
- Klíčová slova
- Annelida, CCF, Discrimination, Earthworm, Immunity, LBP, PAMP, PRR, Phenoloxidase cascade, TLR,
- MeSH
- kroužkovci imunologie MeSH
- membránové glykoproteiny chemie genetika metabolismus MeSH
- PAMP struktury imunologie metabolismus MeSH
- přirozená imunita * MeSH
- proteiny akutní fáze chemie genetika metabolismus MeSH
- receptory rozpoznávající vzory chemie genetika metabolismus MeSH
- regulace genové exprese MeSH
- signální transdukce imunologie MeSH
- tkáňová distribuce MeSH
- toll-like receptory chemie genetika metabolismus MeSH
- transportní proteiny chemie genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- lipopolysaccharide-binding protein MeSH Prohlížeč
- membránové glykoproteiny MeSH
- PAMP struktury MeSH
- proteiny akutní fáze MeSH
- receptory rozpoznávající vzory MeSH
- toll-like receptory MeSH
- transportní proteiny MeSH
Pattern-recognition receptors (PRRs) recognize pathogen-associated molecular patterns and play an important role in triggering innate immune responses. PRRs distribution and function is well documented in mice and humans, but studies in pigs are scarce. Salmonella enterica serovar Typhimurium is common pathogen found in pigs and was used as a model for interaction with PRRs. This study investigated expression of PRRs in porcine leukocyte subpopulations at the mRNA level. Eight subpopulations of leukocytes comprising NK cells, Th, Tc, double positive T cells and γδ T cells, B cells, monocytes and neutrophils were sorted, and the expression of 12 PRRs was measured, including selected Toll-like receptors and their co-receptors, NOD-like receptor NOD2, RP-105, CD14, and dectin. The highest expression rates of most PRRs were observed in monocytes and neutrophils. The B cells expressed high levels of TLR1, TLR6, TLR9, TLR10, and RP-105. Only monocytes and γδ T cells were found to respond to Salmonella enterica serovar Typhimurium infection by intensification of PRRs expression. In Th and B cells, PRRs mRNA down-regulation was detected after infection.
- Klíčová slova
- Leukocyte, Pattern-recognition receptors, Pig, Salmonella, Toll-like receptors,
- MeSH
- down regulace MeSH
- leukocyty metabolismus mikrobiologie MeSH
- messenger RNA genetika MeSH
- neutrofily metabolismus MeSH
- prasata MeSH
- přirozená imunita MeSH
- receptory rozpoznávající vzory genetika metabolismus MeSH
- regulace genové exprese imunologie MeSH
- Salmonella typhimurium fyziologie MeSH
- salmonelová infekce u zvířat imunologie MeSH
- séroskupina MeSH
- T-lymfocyty metabolismus MeSH
- toll-like receptory genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- messenger RNA MeSH
- receptory rozpoznávající vzory MeSH
- toll-like receptory MeSH
Age-related decline in immunity is characterized by stem cell exhaustion, telomere shortening, and disruption of cell-to-cell communication, leading to increased patient risk of disease. Recent data have demonstrated that chronic inflammation exerts a strong influence on immune aging and is closely correlated with telomere length in a range of major pathologies. The current review discusses the impact of inflammation on immune aging, the likely molecular mediators of this process, and the various disease states that have been linked with immunosenescence. Emerging findings implicate NF-κB, the major driver of inflammatory signaling, in several processes that regulate telomere maintenance and/or telomerase activity. While prolonged triggering of pattern recognition receptors is now known to promote immunosenescence, it remains unclear how this process is linked with the telomere complex or telomerase activity. Indeed, enzymatic control of telomere length has been studied for many decades, but alternative roles of telomerase and potential influences on inflammatory responses are only now beginning to emerge. Crosstalk between these pathways may prove to be a key molecular mechanism of immunosenescence. Understanding how components of immune aging interact and modify host protection against pathogens and tumors will be essential for the design of new vaccines and therapies for a wide range of clinical scenarios.
- Klíčová slova
- NF-κB, inflammaging, myelopoiesis, pattern recognition receptor signaling, telomere shortening, toll-like receptor signaling,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), that promotes pulmonary type 2 immunity. Mechanistically, SAA1 interacted directly with allergenic mite FABPs (Der p 13 and Blo t 13). The interaction between mite FABPs and SAA1 activated the SAA1-binding receptor, formyl peptide receptor 2 (FPR2), which drove the epithelial release of the type-2-promoting cytokine interleukin (IL)-33 in a SAA1-dependent manner. Importantly, the SAA1-FPR2-IL-33 axis was upregulated in nasal epithelial cells from patients with chronic rhinosinusitis. These findings identify an unrecognized role for SAA1 as a soluble pattern recognition receptor for conserved FABPs found in common mite allergens that initiate type 2 immunity at mucosal surfaces.
- MeSH
- alergeny imunologie MeSH
- alergická rýma imunologie patologie MeSH
- antigeny roztočů domácího prachu imunologie MeSH
- bronchiální astma imunologie patologie MeSH
- dospělí MeSH
- epitelové buňky MeSH
- humorální imunita MeSH
- interleukin 33 metabolismus MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- modely nemocí na zvířatech MeSH
- myši knockoutované MeSH
- myši MeSH
- plíce cytologie imunologie patologie MeSH
- primární buněčná kultura MeSH
- přirozená imunita MeSH
- proteiny vázající mastné kyseliny imunologie MeSH
- receptory lipoxinů metabolismus MeSH
- receptory pro formylované peptidy metabolismus MeSH
- respirační sliznice imunologie metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sérový amyloid A genetika metabolismus MeSH
- signální transdukce imunologie MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- alergeny MeSH
- antigeny roztočů domácího prachu MeSH
- formyl peptide receptor 2, mouse MeSH Prohlížeč
- FPR2 protein, human MeSH Prohlížeč
- IL33 protein, human MeSH Prohlížeč
- Il33 protein, mouse MeSH Prohlížeč
- interleukin 33 MeSH
- proteiny vázající mastné kyseliny MeSH
- receptory lipoxinů MeSH
- receptory pro formylované peptidy MeSH
- SAA1 protein, human MeSH Prohlížeč
- Saa2 protein, mouse MeSH Prohlížeč
- sérový amyloid A MeSH
Primary interaction of an intracellular bacterium with its host cell is initiated by activation of multiple signaling pathways in response to bacterium recognition itself or as cellular responses to stress induced by the bacterium. The leading molecules in these processes are cell surface membrane receptors as well as cytosolic pattern recognition receptors recognizing pathogen-associated molecular patterns or damage-associated molecular patterns induced by the invading bacterium. In this review, we demonstrate possible sequences of events leading to recognition of Francisella tularensis, present findings on known mechanisms for manipulating cell responses to protect Francisella from being killed, and discuss newly published data from the perspective of early stages of host-pathogen interaction.
- Klíčová slova
- Francisella tularensis, innate immune recognition, intracellular replication, phagocytosis, signaling pathways,
- MeSH
- alarminy genetika imunologie MeSH
- bakteriální proteiny genetika imunologie MeSH
- fagocytóza genetika MeSH
- Francisella tularensis genetika imunologie patogenita MeSH
- interakce hostitele a patogenu genetika imunologie MeSH
- lidé MeSH
- makrofágy imunologie mikrobiologie MeSH
- PAMP struktury imunologie metabolismus MeSH
- přirozená imunita * MeSH
- receptory buněčného povrchu genetika imunologie MeSH
- receptory rozpoznávající vzory genetika imunologie MeSH
- regulace genové exprese MeSH
- signální transdukce MeSH
- tularemie genetika imunologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- alarminy MeSH
- bakteriální proteiny MeSH
- PAMP struktury MeSH
- receptory buněčného povrchu MeSH
- receptory rozpoznávající vzory MeSH
Diseases caused by pathogens contribute to molecular adaptations in host immunity. Variety of viral pathogens challenging animal immunity can drive positive selection diversifying receptors recognising the infections. However, whether distinct virus sensing systems differ across animals in their evolutionary modes remains unclear. Our review provides a comparative overview of natural selection shaping molecular evolution in vertebrate viral-binding pattern recognition receptors (PRRs). Despite prevailing negative selection arising from the functional constraints, multiple lines of evidence now suggest diversifying selection in the Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs) and oligoadenylate synthetases (OASs). In several cases, location of the positively selected sites in the ligand-binding regions suggests effects on viral detection although experimental support is lacking. Unfortunately, in most other PRR families including the AIM2-like receptor family, C-type lectin receptors (CLRs), and cyclic GMP-AMP synthetase studies characterising their molecular evolution are rare, preventing comparative insight. We indicate shared characteristics of the viral sensor evolution and highlight priorities for future research.
- Klíčová slova
- Evolutionary adaptation, Innate immunity, Molecular evolution, Pattern recognition receptor, Positive selection, Virus detection,
- MeSH
- molekulární evoluce MeSH
- obratlovci MeSH
- přirozená imunita * MeSH
- receptory rozpoznávající vzory * genetika MeSH
- selekce (genetika) MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- receptory rozpoznávající vzory * MeSH
In a context of a sustainable viticulture, the implementation of innovative eco-friendly strategies, such as elicitor-triggered immunity, requires a deep knowledge of the molecular mechanisms underlying grapevine defense activation, from pathogen perception to resistance induction. During plant-pathogen interaction, the first step of plant defense activation is ensured by the recognition of microbe-associated molecular patterns, which are elicitors directly derived from pathogenic or beneficial microbes. Vitis vinifera, like other plants, can perceive elicitors of different nature, including proteins, amphiphilic glycolipid, and lipopeptide molecules as well as polysaccharides, thanks to their cognate pattern recognition receptors, the discovery of which recently began in this plant species. Furthermore, damage-associated molecular patterns are another class of elicitors perceived by V. vinifera as an invader's hallmark. They are mainly polysaccharides derived from the plant cell wall and are generally released through the activity of cell wall-degrading enzymes secreted by microbes. Elicitor perception and subsequent activation of grapevine immunity end in some cases in efficient grapevine resistance against pathogens. Using complementary approaches, several molecular markers have been identified as hallmarks of this induced resistance stage. This review thus focuses on the recognition of elicitors by Vitis vinifera describing the molecular mechanisms triggered from the elicitor perception to the activation of immune responses. Finally, we discuss the fact that the link between elicitation and induced resistance is not so obvious and that the formulation of resistance inducers remains a key step before their application in vineyards.
Plants are continuously monitoring the presence of microorganisms to establish an adapted response. Plants commonly use pattern recognition receptors (PRRs) to perceive microbe- or pathogen-associated molecular patterns (MAMPs/PAMPs) which are microorganism molecular signatures. Located at the plant plasma membrane, the PRRs are generally receptor-like kinases (RLKs) or receptor-like proteins (RLPs). MAMP detection will lead to the establishment of a plant defense program called MAMP-triggered immunity (MTI). In this review, we overview the RLKs and RLPs that assure early recognition and control of pathogenic or beneficial bacteria. We also highlight the crucial function of PRRs during plant-microbe interactions, with a special emphasis on the receptors of the bacterial flagellin and peptidoglycan. In addition, we discuss the multiple strategies used by bacteria to evade PRR-mediated recognition.
- Klíčová slova
- FLS2, LysM, MAMP, PRR, evasion, flg22, innate immunity, plant–microbe interactions,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Neutrophils are innate immune cells with important roles in antimicrobial defense. However, impaired or dysregulated neutrophil function can result in host tissue damage, loss of homeostasis, hyperinflammation or pathological immunosuppression. A central link between neutrophil activation and immune outcomes is emerging to be the calcineurin-nuclear factor of activated T cells (NFAT) signaling pathway, which is activated by neutrophil detection of a microbial threat via pattern recognition receptors and results in inflammatory cytokine production. This potent pro-inflammatory pathway is also the target of several immunosuppressive drugs used for the treatment of autoimmune disorders, during solid organ and hematopoietic cell transplantations, and as a part of anti-cancer therapy: but what effects these drugs have on neutrophil function, and their broader consequences for immune homeostasis and microbial defense are not yet known. Here, we bring together the emerging literature describing pathology- and drug- induced neutrophil impairment, with particular focus on their effects on calcineurin-NFAT signaling in the innate immune compartment.
- Klíčová slova
- NFAT signaling, calcineurin inbibitors, immunosuppression, neutrophil (PMN) function, pattern recognition receptor (PRR), sepsis,
- MeSH
- cytokiny imunologie metabolismus MeSH
- homeostáza imunologie MeSH
- imunologická tolerance imunologie MeSH
- kalcineurin imunologie metabolismus MeSH
- lidé MeSH
- mediátory zánětu imunologie metabolismus MeSH
- neutrofily imunologie metabolismus MeSH
- přirozená imunita imunologie MeSH
- receptory rozpoznávající vzory imunologie metabolismus MeSH
- signální transdukce imunologie MeSH
- transkripční faktory NFATC imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cytokiny MeSH
- kalcineurin MeSH
- mediátory zánětu MeSH
- receptory rozpoznávající vzory MeSH
- transkripční faktory NFATC MeSH
The scavenger receptor cysteine-rich (SRCR) family comprises a group of membrane-attached or secreted proteins that contain one or more modules/domains structurally similar to the membrane distal domain of type I macrophage scavenger receptor. Although no all-inclusive biological function has been ascribed to the SRCR family, some of these receptors have been shown to recognize pathogen-associated molecular patterns (PAMP) of bacteria, fungi, or other microbes. SSc5D is a recently described soluble SRCR receptor produced by monocytes/macrophages and T lymphocytes, consisting of an N-terminal portion, which contains five SRCR modules, and a large C-terminal mucin-like domain. Toward establishing a global common role for SRCR domains, we interrogated whether the set of five SRCR domains of SSc5D displayed pattern recognition receptor (PRR) properties. For that purpose, we have expressed in a mammalian expression system the N-terminal SRCR-containing moiety of SSc5D (N-SSc5D), thus excluding the mucin-like domain likely by nature to bind microorganisms, and tested the capacity of the SRCR functional groups to physically interact with bacteria. Using conventional protein-bacteria binding assays, we showed that N-SSc5D had a superior capacity to bind to Escherichia coli strains RS218 and IHE3034 compared with that of the extracellular domains of the SRCR proteins CD5 and CD6 (sCD5 and sCD6, respectively), and similar E. coli-binding properties as Spα, a proven PRR of the SRCR family. We have further designed a more sensitive, real-time, and label-free surface plasmon resonance (SPR)-based assay and examined the capacity of N-SSc5D, Spα, sCD5, and sCD6 to bind to different bacteria. We demonstrated that N-SSc5D compares with Spα in the capacity to bind to E. coli and Listeria monocytogenes, and further that it can distinguish between pathogenic E. coli RS218 and IHE3034 strains and the non-pathogenic laboratory E. coli strain BL21(DE3). Our work thus advocates the utility of SPR-based assays as sensitive tools for the rapid screening of interactions between immune-related receptors and PAMP-bearing microbes. The analysis of our results suggests that SRCR domains of different members of the family have a differential capacity to interact with bacteria, and further that the same receptor can discriminate between different bacteria strains and species.
- Klíčová slova
- bacteria, pattern recognition receptors, scavenger receptor cysteine-rich, surface plasmon resonance,
- Publikační typ
- časopisecké články MeSH