يعرض 1 - 10 نتائج من 11 نتيجة بحث عن '"Pattern recognition receptors (PRRs)"', وقت الاستعلام: 1.06s تنقيح النتائج
  1. 1

    المصدر: International Journal of Molecular Sciences
    Volume 21
    Issue 11
    Fischer, L, Lucendo Villarin, B, Hay, D & O'Farrelly, C 2020, ' Human PSC-derived hepatocytes express low levels of viral pathogen recognition receptors, but are capable of mounting an effective innate immune response ', International Journal of Molecular Sciences, vol. 21, no. 11, 3831 . https://doi.org/10.3390/ijms21113831
    International Journal of Molecular Sciences, Vol 21, Iss 3831, p 3831 (2020)

    الوصف: Hepatocytes are key players in the innate immune response to liver pathogens but are challenging to study because of inaccessibility and a short half-life. Recent advances in in vitro differentiation of hepatocyte-like cells (HLCs) facilitated studies of hepatocyte&ndash
    pathogen interactions. Here, we aimed to define the anti-viral innate immune potential of human HLCs with a focus on toll-like receptor (TLR)-expression and the presence of a metabolic switch. We analysed cytoplasmic pattern recognition receptor (PRR)- and endosomal TLR-expression and activity and adaptation of HLCs to an inflammatory environment. We found that transcript levels of retinoic acid inducible gene I (RIG-I), melanoma differentiation antigen 5 (MDA5), and TLR3 became downregulated during differentiation, indicating the acquisition of a more tolerogenic phenotype, as expected in healthy hepatocytes. HLCs responded to activation of RIG-I by producing interferons (IFNs) and IFN-stimulated genes. Despite low-level expression of TLR3, receptor expression was upregulated in an inflammatory environment. TLR3 signalling induced expression of proinflammatory cytokines at the gene level, indicating that several PRRs need to interact for successful innate immune activation. The inflammatory responsiveness of HLCs was accompanied by the downregulation of cytochrome P450 3A and 1A2 activity and decreased serum protein production, showing that the metabolic switch seen in primary hepatocytes during anti-viral responses is also present in HLCs.

    وصف الملف: application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document

  2. 2

    المصدر: Frontiers in Immunology, Vol 10 (2019)
    Frontiers in Immunology

    الوصف: Pattern recognition receptors (PRRs) coordinate the innate immune response and have a significant role in the development of multiple sclerosis (MS). Accumulating evidence has identified both pathogenic and protective functions of PRR signaling in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Additionally, evidence for PRR signaling in non-immune cells and PRR responses to host-derived endogenous ligands has also revealed new pathways controlling the development of CNS autoimmunity. Many PRRs remain uncharacterized in MS and EAE, and understanding the distinct triggers and functions of PRR signaling in CNS autoimmunity requires further investigation. In this brief review, we discuss the diverse pathogenic and protective functions of PRRs in MS and EAE, and highlight major avenues for future research.

  3. 3

    المصدر: Redox Biology
    Redox Biology, Vol 14, Iss, Pp 250-260 (2018)

    مصطلحات موضوعية: 0301 basic medicine, MAPK/ERK pathway, iC3b, complement C3 fragment, Parkinson's disease, Aβ, β-amyloid, Clinical Biochemistry, PD, Parkinson's disease, Biochemistry, Rats, Sprague-Dawley, Scavenger receptors, chemistry.chemical_compound, 0302 clinical medicine, Neuroinflammation, Paraquat, MPP+, 1-methyl-4-phenyl-pyridium iodide, DEPs, diesel exhaust particles, lcsh:QH301-705.5, Cells, Cultured, CR3, lcsh:R5-920, NADPH oxidase, SN, subsantia nigra, Kinase, Neurodegeneration, Dopaminergic, Cell biology, src-Family Kinases, NADPH Oxidase 2, cardiovascular system, LPS, lipopolysaccharide, Erk, extracellular regulated protein kinases, lcsh:Medicine (General), CAM-1, intercellular adhesion molecule-1, HMGB1, high-mobility group box 1, hormones, hormone substitutes, and hormone antagonists, Research Paper, Signal Transduction, circulatory and respiratory physiology, Proto-oncogene tyrosine-protein kinase Src, MAP Kinase Signaling System, TH, tyrosine hydroxylase, SFKs, Src family kinases, Macrophage-1 Antigen, CR3, complement receptor 3, Biology, CNS, central nervous system, DAMPs, damage associated molecular patterns, 03 medical and health sciences, Iba-1, ionized calcium binding adaptor molecule 1, SOD, superoxide dismutase, medicine, PRRs, pattern recognition receptors (PRRs), Animals, Parkinson Disease, Secondary, Pesticides, urogenital system, Dopaminergic Neurons, Nox2, NADPH oxidase, Organic Chemistry, medicine.disease, Enzyme Activation, Mice, Inbred C57BL, 030104 developmental biology, lcsh:Biology (General), oxLDL, oxidized low-density lipoprotein, chemistry, biology.protein, DHE, dihydroethidium, PAMPs, pathogen associated molecular patterns, 030217 neurology & neurosurgery

    الوصف: Microglial NADPH oxidase (Nox2) plays a key role in chronic neuroinflammation and related dopaminergic neurodegeneration in Parkinson's disease (PD). However, the mechanisms behind Nox2 activation remain unclear. Here, we revealed the critical role of complement receptor 3 (CR3), a microglia-specific pattern recognition receptor, in Nox2 activation and subsequent dopaminergic neurodegeneration by using paraquat and maneb-induced PD model. Suppression or genetic deletion of CR3 impeded paraquat and maneb-induced activation of microglial Nox2, which was associated with attenuation of dopaminergic neurodegeneration. Mechanistic inquiry revealed that blocking CR3 reduced paraquat and maneb-induced membrane translocation of Nox2 cytosolic subunit p47phox, an essential step for Nox2 activation. Src and Erk (extracellular regulated protein kinases) were subsequently recognized as the downstream signals of CR3. Moreover, inhibition of Src or Erk impaired Nox2 activation in response to paraquat and maneb co-exposure. Finally, we found that CR3-deficient mice were more resistant to paraquat and maneb-induced Nox2 activation and nigral dopaminergic neurodegeneration as well as motor dysfunction than the wild type controls. Taken together, our results showed that CR3 regulated Nox2 activation and dopaminergic neurodegeneration through a Src-Erk-dependent pathway in a two pesticide-induced PD model, providing novel insights into the immune pathogenesis of PD.
    Highlights • CR3, but not SRs is capable of mediating NOX2 activation in experimental PD. • CR3 regulates NOX2 activation via a Src-Erk-dependent manner. • Blocking CR3 ameliorates microglial activation and dopaminergic neurodegeneration.

  4. 4

    المصدر: Frontiers in Immunology, Vol 9 (2019)
    Frontiers in Immunology

    الوصف: Amphibian skin is a mucosal surface in direct and continuous contact with a microbially diverse and laden aquatic and/or terrestrial environment. As such, frog skin is an important innate immune organ and first line of defence against pathogens in the environment. Critical to the innate immune functions of frog skin are the maintenance of physical, chemical, cellular, and microbiological barriers and the complex network of interactions that occur across all the barriers. Despite the global decline in amphibian populations, largely as a result of emerging infectious diseases, we understand little regarding the cellular and molecular mechanisms that underlie the innate immune function of amphibian skin and defence against pathogens. In this review, we discuss the structure, cell composition and cellular junctions that contribute to the skin physical barrier, the antimicrobial peptide arsenal that, in part, comprises the chemical barrier, the pattern recognition receptors involved in recognizing pathogens and initiating innate immune responses in the skin, and the contribution of commensal microbes on the skin to pathogen defence. We briefly discuss the influence of environmental abiotic factors (natural and anthropogenic) and pathogens on the immunocompetency of frog skin defences. Although some aspects of frog innate immunity, such as antimicrobial peptides are well-studied; other components and how they contribute to the skin innate immune barrier, are lacking. Elucidating the complex network of interactions occurring at the interface of the frog's external and internal environments will yield insight into the crucial role amphibian skin plays in host defence and the environmental factors leading to compromised barrier integrity, disease, and host mortality.

  5. 5

    المصدر: Frontiers in Immunology, Vol 9 (2018)
    Frontiers in Immunology
    Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
    Consejería de Sanidad de la Comunidad de Madrid
    Repisalud
    Instituto de Salud Carlos III (ISCIII)

    الوصف: Challenge with specific microbial stimuli induces long lasting epigenetic changes in innate immune cells that result in their enhanced response to a second challenge by the same or unrelated microbial insult, a process referred to as trained immunity. This opens a new avenue in vaccinology to develop Trained Immunity-based Vaccines (TIbV), defined as vaccine formulations that induce training in innate immune cells. Unlike conventional vaccines, which are aimed to elicit only specific responses to vaccine-related antigens, TIbV aim to stimulate broader responses. As trained immunity is generally triggered by pattern recognition receptors (PRRs), TIbV should be formulated with microbial structures containing suitable PRR-ligands. The TIbV concept we describe here may be used for the development of vaccines focused to promote host resistance against a wide spectrum of pathogens. Under the umbrella of trained immunity, a broad protection can be achieved by: (i) increasing the nonspecific effector response of innate immune cells (e.g., monocyte/macrophages) to pathogens, (ii) harnessing the activation state of dendritic cells to enhance adaptive T cell responses to both specific and nonrelated (bystander) antigens. This capacity of TIbV to promote responses beyond their nominal antigens may be particularly useful when conventional vaccines are not available or when multiple coinfections and/or recurrent infections arise in susceptible individuals. As the set of PRR-ligands chosen is essential not only for stimulating trained immunity but also to drive adaptive immunity, the precise design of TIbV will improve with the knowledge on the functional relationship among the different PRRs. While the TIbV concept is emerging, a number of the current anti-infectious vaccines, immunostimulants, and even vaccine adjuvants may already fall in the TIbV category. This may apply to increase immunogenicity of novel vaccine design approaches based on small molecules, like those achieved by reverse vaccinology. Sí

    وصف الملف: application/pdf

  6. 6

    المؤلفون: Johnathan Canton

    المصدر: Frontiers in Immunology
    Frontiers in Immunology, Vol 9 (2018)

    الوصف: Macropinocytosis has received increasing attention in recent years for its various roles in nutrient acquisition, immune surveillance, and virus and cancer pathologies. In most cases macropinocytosis is initiated by the sudden increase in an external stimulus such as a growth factor. This “induced” form of macropinocytosis has been the subject of much of the work addressing its mechanism and function over the years. An alternative, “constitutive” form of macropinocytosis restricted to primary innate immune cells also exists, although its mechanism has remained severely understudied. This mini-review focuses on the very recent advances that have shed new light on the initiation, formation and functional relevance of constitutive macropinocytosis in primary innate immune cells. An emphasis is placed on how this new understanding of constitutive macropinocytosis is helping to define the sentinel function of innate immune cells including polarized macrophages and dendritic cells.

  7. 7

    المصدر: Viruses, Vol 10, Iss 10, p 514 (2018)
    Viruses

    الوصف: The cellular antiviral innate immune response is triggered upon recognition of specific viral components by a set of the host’s cytoplasmic or membrane-bound receptors. This interaction induces specific signaling cascades that culminate with the production of interferons and the expression of interferon-stimulated genes and pro-inflammatory cytokines that act as antiviral factors, suppressing viral replication and restricting infection. Here, we review and discuss the different mechanisms by which each of these receptors is able to recognize and signal infection by the human cytomegalovirus (HCMV), an important human pathogen mainly associated with severe brain defects in newborns and disabilities in immunocompromised individuals. We further present and discuss the many sophisticated strategies developed by HCMV to evade these different signaling mechanisms and counteract the cellular antiviral response, in order to support cell viability and sustain its slow replication cycle.

  8. 8

    المساهمون: Prevete, Nella, de Paulis, Amato, Sgambato, Dolore, Melillo, Rosa Marina, D'Argenio, Giuseppe, Romano, Lorenzo, Zagari, Rocco Maurizio, Romano, Marco, Prevete, N., de Paulis, A., Sgambato, D., Melillo, R. M., D'Argenio, G., Romano, L., Zagari, R. M., Romano, M.

    المصدر: Current pharmaceutical design
    (2018).
    info:cnr-pdr/source/autori:Prevete N, de Paulis A, Sgambato D, Melillo RM, D'Argenio G, Romano L, Zagari RM, Romano M./titolo:Role of Formyl Peptide Receptors In Gastrointestinal Healing./doi:/rivista:Current pharmaceutical design (Print)/anno:2018/pagina_da:/pagina_a:/intervallo_pagine:/volume

    الوصف: The wound healing and the barrier restoration of the gastrointestinal (GI) mucosa must be continuously ensured to allow homeostasis of the gastrointestinal tract and of all the surrounding tissues. Several lines of the evidence report a key role of innate immunity, and in particular of Pattern Recognition Receptors (PRRs), in controlling the homeostasis of GI tract by sensing commensal and pathogen bacteria, activating the immune response and regulating epithelial repair, thus guaranteeing the morphological and functional recovery of the injured tissue. We will discuss the role of a particular class of PRRs - the Formyl Peptide Receptors - in the homeostasis of GI mucosa. We here report the results of studies that strongly suggest the possibility that the activation of FPRs is crucial in the maintenance of homeostasis of the GI tract and provide indications of the potential clinical relevance of new treatment regimens involving FPR modulation for several GI disorders.

    وصف الملف: ELETTRONICO

  9. 9

    المصدر: Plant Pattern Recognition Receptors. Humana Press Inc.
    Plant Pattern Recognition Receptors
    Methods in Molecular Biology ISBN: 9781493968589

    الوصف: In modern resistance breeding, effectors have emerged as tools for accelerating and improving the identification of immune receptors. Effector-assisted breeding was pioneered for identifying resistance genes (R genes) against Phytophthora infestans in potato (Solanum tuberosum). Here we show that effectoromics approaches are also well suitable for identifying pathogen recognition receptors (PRRs) that recognize apoplastic effectors. To detect genotypes that recognize apoplastic proteins of P. infestans, routine agroinfiltration and potato virus X (PVX) agroinfection methods can be applied. In addition, protein infiltrations are feasible for assessing responses to apoplastic effectors and aid in confirming results obtained from the aforementioned methods. Protocols for the effectoromics pipeline are provided, starting from phenotyping for effector responses, up to genotyping and PRR gene identification.

    وصف الملف: application/octet-stream; application/pdf

  10. 10

    المصدر: BMC Plant Biology
    BMC plant biology, 16:31

    الوصف: Background Calcium, as a second messenger, transduces extracellular signals into cellular reactions. A rise in cytosolic calcium concentration is one of the first plant responses after exposure to microbe-associated molecular patterns (MAMPs). We reported previously the isolation of Arabidopsis thaliana mutants with a “changed calcium elevation” (cce) response to flg22, a 22-amino-acid MAMP derived from bacterial flagellin. Results Here, we characterized the cce2 mutant and its weaker allelic mutant, cce3. Besides flg22, the mutants respond with a reduced calcium elevation to several other MAMPs and a plant endogenous peptide that is proteolytically processed from pre-pro-proteins during wounding. Downstream defense-related events such flg22-induced mitogen-activated protein kinase activation, accumulation of reactive oxygen species and growth arrest are also attenuated in cce2/cce3. By genetic mapping, next-generation sequencing and allelism assay, CCE2/CCE3 was identified to be ALG3 (Asparagine-linked glycosylation 3). This encodes the α-1,3-mannosyltransferase responsible for the first step of core oligosaccharide Glc3Man9GlcNAc2 glycan assembly on the endoplasmic reticulum (ER) luminal side. Complementation assays and glycan analysis in yeast alg3 mutant confirmed the reduced enzymatic function of the proteins encoded by the cce2/cce3 alleles – leading to accumulation of M5ER, the immature five mannose-containing oligosaccharide structure found in the ER. Proper protein glycosylation is required for ER/Golgi processing and trafficking of membrane proteins to the plasma membrane. Endoglycosidase H-insensitivity of flg22 receptor, FLS2, in the cce2/cce3 mutants suggests altered glycan structures in the receptor. Conclusion Proper glycosylation of MAMP receptors (or other exported proteins) is required for optimal responses to MAMPs and is important for immune signaling of host plants. Electronic supplementary material The online version of this article (doi:10.1186/s12870-016-0718-3) contains supplementary material, which is available to authorized users.

    وصف الملف: application/pdf