11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The inflammasomes, immune guardians at defence barriers

      review-article
      1 , 2 , , 2 , 3
      Immunology
      John Wiley and Sons Inc.
      epithelial cell, inflammasome, inflammation

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          As a result of its strategic location, the epithelium is constantly exposed to a wide variety of pathogen and danger signals. Traditionally, the epithelium has been perceived as a defensive but passive barrier; however, it has now become evident that the epithelium senses and actively responds to these signals in order to maintain barrier homeostasis and contributes to the inflammatory response. One way it does this is by producing pro‐inflammatory cytokines including interleukin‐1 β ( IL‐1 β) and IL‐18. These two cytokines are synthesized as inactive precursors, the maturation of which is mediated by pro‐inflammatory caspases after the activation and assembly of macromolecular complexes called inflammasomes. Epithelial cells express a large panel of inflammasome components, and although the molecular mechanisms underlying the activation of these complexes in haematopoietic cells are well understood, how epithelial cells react to danger signals to activate the inflammasome remains unclear. We review and discuss how different inflammasomes contribute to barrier homeostasis and inflammation at several barrier sites, their mechanisms and how their aberrant regulation contributes to disease at the different epithelia.

          Related collections

          Most cited references92

          • Record: found
          • Abstract: found
          • Article: not found

          Recognition of single-stranded RNA viruses by Toll-like receptor 7.

          Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death

            Abstract Pyroptosis is a lytic type of cell death that is initiated by inflammatory caspases. These caspases are activated within multi‐protein inflammasome complexes that assemble in response to pathogens and endogenous danger signals. Pyroptotic cell death has been proposed to proceed via the formation of a plasma membrane pore, but the underlying molecular mechanism has remained unclear. Recently, gasdermin D (GSDMD), a member of the ill‐characterized gasdermin protein family, was identified as a caspase substrate and an essential mediator of pyroptosis. GSDMD is thus a candidate for pyroptotic pore formation. Here, we characterize GSDMD function in live cells and in vitro. We show that the N‐terminal fragment of caspase‐1‐cleaved GSDMD rapidly targets the membrane fraction of macrophages and that it induces the formation of a plasma membrane pore. In vitro, the N‐terminal fragment of caspase‐1‐cleaved recombinant GSDMD tightly binds liposomes and forms large permeability pores. Visualization of liposome‐inserted GSDMD at nanometer resolution by cryo‐electron and atomic force microscopy shows circular pores with variable ring diameters around 20 nm. Overall, these data demonstrate that GSDMD is the direct and final executor of pyroptotic cell death.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages

              The interleukin-1 (IL-1) family cytokines are cytosolic proteins that exhibit inflammatory activity upon release into the extracellular space. These factors are released following various cell death processes, with pyroptosis being a common mechanism. Recently, it was recognized that phagocytes can achieve a state of hyperactivation, which is defined by their ability to secrete IL-1 while retaining viability, yet it is unclear how IL-1 can be secreted from living cells. Herein, we report that the pyroptosis regulator gasdermin D (GSDMD) was necessary for IL-1β secretion from living macrophages that have been exposed to inflammasome activators, such as bacteria and their products or host-derived oxidized lipids. Cell- and liposome-based assays demonstrated that GSDMD pores were required for IL-1β transport across an intact lipid bilayer. These findings identify a non-pyroptotic function for GSDMD, and raise the possibility that GSDMD pores represent conduits for the secretion of cytosolic cytokines under conditions of cell hyperactivation.
                Bookmark

                Author and article information

                Contributors
                pablo.palazon-riquelme@ens-lyon.fr
                Journal
                Immunology
                Immunology
                10.1111/(ISSN)1365-2567
                IMM
                Immunology
                John Wiley and Sons Inc. (Hoboken )
                0019-2805
                1365-2567
                06 September 2018
                November 2018
                06 September 2018
                : 155
                : 3 ( doiID: 10.1111/imm.2018.155.issue-3 )
                : 320-330
                Affiliations
                [ 1 ] International Centre for Infectiology Research INSERM U1111 CNRS UMR5308 École Normale Supérieure de Lyon Claude Bernard Lyon 1 University Lyon France
                [ 2 ] Manchester Collaborative Centre of Inflammation Research The University of Manchester Manchester UK
                [ 3 ] The Lydia Becker Institute of Immunology and Inflammation Faculty of Biology, Medicine and Health Manchester Academic Health Sciences Centre University of Manchester Manchester UK
                Author notes
                [*] [* ] Correspondence: Pablo Palazon‐Riquelme, International Centre for Infectiology Research, INSERM U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Claude Bernard Lyon 1 University, 69007 Lyon, France. Email: pablo.palazon-riquelme@ 123456ens-lyon.fr

                Senior author: Gloria Lopez‐Castejon

                Author information
                http://orcid.org/0000-0001-6799-2698
                Article
                IMM12989
                10.1111/imm.12989
                6187212
                30098204
                a8e3b322-ee08-4238-be0f-1d654237faa5
                © 2018 The Authors. Immunology Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 01 May 2018
                : 12 July 2018
                : 27 July 2018
                Page count
                Figures: 2, Tables: 1, Pages: 11, Words: 10367
                Funding
                Funded by: Sir Henry Dale Fellowship Jointly
                Funded by: the Wellcome Trust and the Royal Society
                Award ID: 104192/Z/14/Z
                Funded by: Manchester Collaborative Centre for Inflammation Research
                Funded by: A Joint Initiative of the University of Manchester
                Funded by: AstraZeneca and GlaxoSmithKline
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                imm12989
                November 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0.1 mode:remove_FC converted:15.10.2018

                Immunology
                epithelial cell,inflammasome,inflammation
                Immunology
                epithelial cell, inflammasome, inflammation

                Comments

                Comment on this article