The Experts below are selected from a list of 168450 Experts worldwide ranked by ideXlab platform

Gabriel Nunez - One of the best experts on this subject based on the ideXlab platform.

  • dysregulation of p38 and mkp 1 in response to nod1 tlr4 stimulation in sarcoid bronchoalveolar cells
    American Journal of Respiratory and Critical Care Medicine, 2011
    Co-Authors: Ruchi Rastogi, Gabriel Nunez, Gaila Pirockinaite, Yusen Liu, Lobelia Samavati
    Abstract:

    Rationale: Sarcoidosis is a systemic inflammatory disorder characterized by distinct up-regulation of Th1 cytokines, such as tumor necrosis factor (TNF)-α and IL-12. The mechanism underlying this up-regulation remains unclear. Recognition of microbial moieties through Toll-like or NOD-like Receptors evokes sequential activation of mitogen-activated protein kinases (MAPKs), which plays a role in Th1-immune response. Objectives: To test the hypothesis that dysregulation in MAPK signaling in response to microbial stimulation is important in mediating Th1 response in sarcoidosis.Methods: Ex vivo cultured bronchoalveolar lavage (BAL) cells isolated from patients with sarcoidosis and control subjects were stimulated with low-dose Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain 1 (NOD1) ligands as a model of microbial stimulation, and MAPK signaling and inflammatory response were analyzed.Measurements and Main Results: BAL cells from patients with sarcoidosis exhibited higher basal p38 ...

  • nod like Receptors role in innate immunity and inflammatory disease
    Annual Review of Pathology-mechanisms of Disease, 2009
    Co-Authors: Grace Y Chen, Michael H. Shaw, Yun Gi Kim, Gabriel Nunez
    Abstract:

    The NOD-like Receptors (NLRs) are a specialized group of intracellular Receptors that represent a key component of the host innate immune system. Since the discovery of the first NLR almost 10 years ago, the study of this special class of microbial sensors has burgeoned; consequently, a better understanding of the mechanism by which these Receptors recognize microbes and other danger signals and of how they activate inflammatory signaling pathways has emerged. Moreover, in addition to their primary role in host defense against invading pathogens, their ability to regulate nuclear factor-kappa B (NF-kappaB) signaling, interleukin-1-beta (IL-1beta) production, and cell death indicates that they are crucial to the pathogenesis of a variety of inflammatory human diseases.

  • the innate immune receptor nod1 protects the intestine from inflammation induced tumorigenesis
    Cancer Research, 2008
    Co-Authors: Grace Y Chen, Michael H. Shaw, Gloria Redondo, Gabriel Nunez
    Abstract:

    There is growing evidence that the host innate immune system has a critical role in regulating carcinogenesis, but the specific Receptors involved and the importance of their interaction with commensal bacteria need to be elucidated. Two major classes of innate immune Receptors, the Toll-like Receptors and NOD-like Receptors, many of which are upstream of nuclear factor-kappaB, are involved in the detection of intestinal bacteria. The Toll-like Receptors have been implicated in promoting colon tumorigenesis, but the role of NOD-like Receptors in regulating tumorigenesis remains unclear. Using an established mouse model system of colitis-associated colon tumorigenesis, we show that Nod1 deficiency results in the increased development of both colitis-associated and Apc tumor suppressor-related colon tumors. In the absence of Nod1 signaling, there is a greater disruption of the intestinal epithelial cell barrier due to chemically induced injury as manifested by increased surface epithelial apoptosis early on during chemically induced colitis and increased intestinal permeability. The increased intestinal permeability is associated with enhanced inflammatory cytokine production and epithelial cell proliferation in Nod1-deficient mice as compared with wild-type mice. Depletion of the gut microbiota suppressed tumor development in Nod1-deficient mice, thus highlighting a link between the commensal bacteria within the intestine and the host innate immune Nod1 signaling pathway in the regulation inflammation-mediated colon cancer development.

  • NOD-like Receptors (NLRs): bona fide intracellular microbial sensors.
    Current Opinion in Immunology, 2008
    Co-Authors: Michael H. Shaw, Thornik Reimer, Gabriel Nunez
    Abstract:

    The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) (nucleotide-binding domain leucine-rich repeat containing) family of proteins has been demonstrated to function as regulators of innate immune response against microbial pathogens. Stimulation of NOD1 and NOD2, two prototypic NLRs, results in the activation of MAPK and NF-κB. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of an inflammasome. This review discusses recent findings regarding the signaling pathways utilized by NLR proteins in the control of caspase-1 and NF-κB activation, as well as the nonredundant role of NLRs in pathogen clearance. The review also covers advances regarding the cellular localization of these proteins and the implications this may have on pathogen sensing and signal transduction.

  • Intracellular NOD-like Receptors in Host Defense and Disease
    Immunity, 2007
    Co-Authors: Thirumala-devi Kanneganti, Mohamed Lamkanfi, Gabriel Nunez
    Abstract:

    The innate immune system comprises several classes of pattern recognition Receptors, including Toll-like Receptors (TLRs), NOD-like Receptors (NLRs), and RIG-1-like Receptors (RLRs). TLRs recognize microbes on the cell surface and in endosomes, whereas NLRs and RLRs detect microbial components in the cytosol. Here we discuss the recent understanding in NLRs. Two NLRs, NOD1 and NOD2, sense the cytosolic presence of the peptidoglycan fragments meso-DAP and muramyl dipeptide, respectively, and drive the activation of mitogen-activated protein kinase (MAPK) and the transcription factor NF-κB. A different set of NLRs induces caspase-1 activation through the assembly of large protein complexes named inflammasomes. Genetic variations in several NLR members are associated with the development of inflammatory disorders. Further understanding of NLRs should provide new insights into the mechanisms of host defense and the pathogenesis of inflammatory diseases.

Lars-olaf Cardell - One of the best experts on this subject based on the ideXlab platform.

  • innate immune Receptors in human airway smooth muscle cells activation by tlr1 2 tlr3 tlr4 tlr7 and nod1 agonists
    PLOS ONE, 2013
    Co-Authors: Anne Månsson Kvarnhammar, Lotta Tengroth, Mikael Adner, Lars-olaf Cardell
    Abstract:

    Background Pattern-recognition Receptors (PRRs), including Toll-like Receptors (TLRs), NOD-like Receptors (NLRs) and RIG-I-like Receptors (RLRs), recognize microbial components and trigger a host defense response. Respiratory tract infections are common causes of asthma exacerbations, suggesting a role for PRRs in this process. The present study aimed to examine the expression and function of PRRs on human airway smooth muscle cells (HASMCs).

  • effects of nod like Receptors in human b lymphocytes and crosstalk between nod1 nod2 and toll like Receptors
    Journal of Leukocyte Biology, 2011
    Co-Authors: Terese Petterson, Johan Jendholm, Anne Mansson, Anders Bjartell, Kristian Riesbeck, Lars-olaf Cardell
    Abstract:

    NLRs are recently discovered PRRs detecting substructures of peptidoglycans and triggering innate immunity. NLRs are expressed in several cell types, but the presence in human B lymphocytes is still unknown. This study aimed to investigate expression and function of NLRs in human B lymphocytes. B cells were isolated and analyzed for mRNA and protein expression. The functional responsiveness of NOD1 and NOD2 was investigated upon stimulation with the cognate ligands, with or without stimulation via IgM/IgD/CD40 and/or selected TLR agonists. A differential expression of NLRs was demonstrated in blood-derived and tonsillar B cells, whereas no variations were found among naive, germinal center, or memory B cells. Stimulation with the ligands alone did not induce B cell activation. However, upon concomitant BCR triggering, an increase in proliferation was seen, together with an induction of cell surface markers (CD27, CD69, CD71, CD80, CD86, and CD95) and prolonged survival. Peripheral B cells were activated by NOD1 and NOD2 ligands, whereas tonsil-derived B cells responded solely to NOD1. In contrast, costimulation with CD40L failed to induce activation. Additionally, it was found that NLR ligands could enhance TLR-induced proliferation of B cells. The present study demonstrates expression of functional NLRs in human B cells. We show that NOD1 and NOD2 have the ability to augment the BCR-induced activation independently of physical T cell help. Hence, NLRs represent a new pathway for B cell activation and a potentially important system of a host defense role against bacterial infections. (Less)

Lei Wang - One of the best experts on this subject based on the ideXlab platform.

  • the transcriptomic response to copper exposure in the digestive gland of japanese scallops mizuhopecten yessoensis
    Fish & Shellfish Immunology, 2015
    Co-Authors: Xiaolin Meng, Mei Liu, Baojie Wang, Keyong Jiang, Xue Tian, Guoxing Nie, Junli Wang, Qianqian Guo, Jianrong Huang, Lei Wang
    Abstract:

    The present study was conducted to elucidate the effects of copper exposure on the immune system and lipid metabolism of the Japanese scallop, Mizuhopecten yessoensts. Transcriptional levels of differentially expressed genes (DEGs)in M. yessoensis digestive gland tissue were analyzed using the deep-sequencing platform Illumina HiSeq (TM) 2000. In total, 841 and 877 genes were identified as significantly up- or down-regulated, respectively. In addition, significant enrichment analysis identified 3 gene ontology terms and 15 pathways involved in the response to copper exposure. Analysis of transcripts related to the immune response revealed a complex pattern of innate recognition Receptors, including toll-like Receptors, NOD-like Receptors and downstream pathway effectors, including those involved in apoptosis. Furthermore, genomic analysis revealed that genes involved in extracellular matrix (ECM)-receptor interactions were enriched in Cu-exposed scallop glands. These results will provide a resource for subsequent gene expression studies regarding heavy metal exposure and the identification of copper-sensitive biomarkers for the aquaculture of M. yessoensis. (C) 2015 Elsevier Ltd. All rights reserved.

  • the transcriptomic response to copper exposure by the gill tissue of japanese scallops mizuhopecten yessoensis using deep sequencing technology
    Fish & Shellfish Immunology, 2014
    Co-Authors: Xiaolin Meng, Mei Liu, Baojie Wang, Keyong Jiang, Xue Tian, Guoxing Nie, Lei Wang
    Abstract:

    The bivalve Mizuhopecten yessoensis has been greatly impacted by marine pollutants in northern China. To elucidate the toxicological mechanism of copper exposure on the immune system, we investigated differentially expressed genes (DEGs) and transcript abundance in M. yessoensis gill tissue using the deep-sequencing platform Illumina HiSeq™ 2000. In total, 1312 and 2237 genes were identified as significantly up- or down-regulated, respectively. In addition, significant enrichment analysis identified 9 GO terms and 38 pathways involved in the response to copper exposure. The analysis of immune-related transcripts revealed a complex repertoire of innate recognition Receptors, including toll-like Receptors, NOD-like Receptors and RIG-like Receptors. Downstream pathway effectors, such as apoptotic, lysosomal and C-type lectin transcripts, were also analyzed. These results will provide a resource for subsequent gene expression studies regarding heavy metal exposure and the identification of copper-sensitive biomarkers to monitor the aquaculture of M. yessoensis.

Shizuo Akira - One of the best experts on this subject based on the ideXlab platform.

  • toll like Receptors and their crosstalk with other innate Receptors in infection and immunity
    Immunity, 2011
    Co-Authors: Taro Kawai, Shizuo Akira
    Abstract:

    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.

  • pathogen recognition by the innate immune system
    International Reviews of Immunology, 2011
    Co-Authors: Himanshu Kumar, Taro Kawai, Shizuo Akira
    Abstract:

    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 pathwa...

  • Identification and functions of pattern-recognition Receptors
    The Journal of allergy and clinical immunology, 2010
    Co-Authors: Yutaro Kumagai, Shizuo Akira
    Abstract:

    Since the identification of Toll-like Receptors, our knowledge about pattern-recognition Receptors (PRRs) has increased rapidly. Classes of PRRs that have been recently discovered include RIG-I–like Receptors, NOD-like Receptors, and C-type lectin Receptors. Recent studies have started to clarify the molecular basis of PRR-ligand interactions, yet the numbers of PRRs and their ligands continue to increase. New technologies have elucidated the network regulation of immune responses at the cellular and in vivo levels. We review the most recent discoveries about PRRs and their ligands, their roles in intracellular and in vivo regulation of immune responses, and the systems biology of innate immunity.

  • pattern recognition Receptors and inflammation
    Cell, 2010
    Co-Authors: Osamu Takeuchi, Shizuo Akira
    Abstract:

    Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition Receptors (PRRs), which include Toll-like Receptors, RIG-I-like Receptors, NOD-like Receptors, and C-type lectin Receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses.

  • innate immunity to virus infection
    Immunological Reviews, 2009
    Co-Authors: Osamu Takeuchi, Shizuo Akira
    Abstract:

    The innate immune system is essential for the initial detection of invading viruses and subsequent activation of adaptive immunity. Three classes of Receptors, designated retinoic acid-inducible gene I (RIG-I)-like Receptors (RLRs), Toll-like Receptors (TLRs), and nucleotide oligomerization domain (NOD)-like Receptors (NLRs), sense viral components, such as double-stranded RNA (dsRNA), single-stranded RNA, and DNA. RLRs and TLRs play essential roles in the production of type I interferons (IFNs) and proinflammatory cytokines in cell type-specific manners. While the RLRs play essential roles in the recognition of RNA viruses in various cells, plasmacytoid dendritic cells utilize TLRs for detecting virus invasion. NLRs play a role in the production of mature interleukin-1 beta to dsRNA stimulation. Activation of innate immune cells is critical for mounting adaptive immune responses. In this review, we discuss recent advances in our understanding of the mechanisms of viral RNA recognition by these different types of Receptors and its relation to acquired immune responses.

Xiaolin Meng - One of the best experts on this subject based on the ideXlab platform.

  • the transcriptomic response to copper exposure in the digestive gland of japanese scallops mizuhopecten yessoensis
    Fish & Shellfish Immunology, 2015
    Co-Authors: Xiaolin Meng, Mei Liu, Baojie Wang, Keyong Jiang, Xue Tian, Guoxing Nie, Junli Wang, Qianqian Guo, Jianrong Huang, Lei Wang
    Abstract:

    The present study was conducted to elucidate the effects of copper exposure on the immune system and lipid metabolism of the Japanese scallop, Mizuhopecten yessoensts. Transcriptional levels of differentially expressed genes (DEGs)in M. yessoensis digestive gland tissue were analyzed using the deep-sequencing platform Illumina HiSeq (TM) 2000. In total, 841 and 877 genes were identified as significantly up- or down-regulated, respectively. In addition, significant enrichment analysis identified 3 gene ontology terms and 15 pathways involved in the response to copper exposure. Analysis of transcripts related to the immune response revealed a complex pattern of innate recognition Receptors, including toll-like Receptors, NOD-like Receptors and downstream pathway effectors, including those involved in apoptosis. Furthermore, genomic analysis revealed that genes involved in extracellular matrix (ECM)-receptor interactions were enriched in Cu-exposed scallop glands. These results will provide a resource for subsequent gene expression studies regarding heavy metal exposure and the identification of copper-sensitive biomarkers for the aquaculture of M. yessoensis. (C) 2015 Elsevier Ltd. All rights reserved.

  • the transcriptomic response to copper exposure by the gill tissue of japanese scallops mizuhopecten yessoensis using deep sequencing technology
    Fish & Shellfish Immunology, 2014
    Co-Authors: Xiaolin Meng, Mei Liu, Baojie Wang, Keyong Jiang, Xue Tian, Guoxing Nie, Lei Wang
    Abstract:

    The bivalve Mizuhopecten yessoensis has been greatly impacted by marine pollutants in northern China. To elucidate the toxicological mechanism of copper exposure on the immune system, we investigated differentially expressed genes (DEGs) and transcript abundance in M. yessoensis gill tissue using the deep-sequencing platform Illumina HiSeq™ 2000. In total, 1312 and 2237 genes were identified as significantly up- or down-regulated, respectively. In addition, significant enrichment analysis identified 9 GO terms and 38 pathways involved in the response to copper exposure. The analysis of immune-related transcripts revealed a complex repertoire of innate recognition Receptors, including toll-like Receptors, NOD-like Receptors and RIG-like Receptors. Downstream pathway effectors, such as apoptotic, lysosomal and C-type lectin transcripts, were also analyzed. These results will provide a resource for subsequent gene expression studies regarding heavy metal exposure and the identification of copper-sensitive biomarkers to monitor the aquaculture of M. yessoensis.