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      Intracellular killing of bacteria: is D ictyostelium a model macrophage or an alien?

      review-article
      * ,
      Cellular Microbiology
      BlackWell Publishing Ltd

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          Abstract

          Predation of bacteria by phagocytic cells was first developed during evolution by environmental amoebae. Many of the core mechanisms used by amoebae to sense, ingest and kill bacteria have also been conserved in specialized phagocytic cells in mammalian organisms. Here we focus on recent results revealing how D ictyostelium discoideum senses and kills non-pathogenic bacteria. In this model, genetic analysis of intracellular killing of bacteria has revealed a surprisingly complex array of specialized mechanisms. These results raise new questions on these processes, and challenge current models based largely on studies in mammalian phagocytes. In addition, recent studies suggest one additional level on complexity by revealing how D ictyostelium recognizes specifically various bacterial species and strains, and adapts its metabolism to process them. It remains to be seen to what extent mechanisms uncovered in D ictyostelium are also used in mammalian phagocytic cells.

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          Most cited references45

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          The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults.

          The cytokine-induced activation cascade of NF-kappaB in mammals and the activation of the morphogen dorsal in Drosophila embryos show striking structural and functional similarities (Toll/IL-1, Cactus/I-kappaB, and dorsal/NF-kappaB). Here we demonstrate that these parallels extend to the immune response of Drosophila. In particular, the intracellular components of the dorsoventral signaling pathway (except for dorsal) and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults. We also show that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection. Antibacterial genes are induced either by a distinct pathway involving the immune deficiency gene (imd) or by combined activation of both imd and dorsoventral pathways.
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            The NRAMP family of metal-ion transporters.

            The family of NRAMP metal ion transporters functions in diverse organisms from bacteria to human. NRAMP1 functions in metal transport across the phagosomal membrane of macrophages, and defective NRAMP1 causes sensitivity to several intracellular pathogens. DCT1 (NRAMP2) transport metal ions at the plasma membrane of cells of both the duodenum and in peripheral tissues, and defective DCT1 cause anemia. The driving force for the metal-ion transport is proton gradient (protonmotive force). In DCT1 the stoichiometry between metal ion and proton varied at different conditions due to a mechanistic proton slip. Though the metal ion transport by Smf1p, the yeast homolog of DCT1, is also a protonmotive force, a slippage of sodium ions was observed. The mechanism of the above phenomena could be explained by a combination between transporter and channel mechanisms.
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              The role of cathelicidins in the innate host defenses of mammals.

              The cathelicidin peptides comprise one of several families of antimicrobial peptides that are found in neutrophils and epithelia as components of the early host defenses of mammals against infection. All cathelicidin family members are synthesized and stored in cells as two-domain proteins. These are split on demand to produce a cathelin protein and an antimicrobial peptide. Accumulating evidence indicates that both the cathelin portion and the C-terminal peptide exert biological activities connected with host protection. This review presents an overview of the structure and biology of cathelicidins and discusses recent progress in cathelicidin research with emphasis on the functional properties and role in host defense of the human cathelicidin hCAP18/LL-37. Although investigators initially concentrated their attention on antibiotic activity, it is becoming clear now that LL-37 is a multifunctional molecule that may mediate various host responses, and thus represents an essential component of the innate immune system in humans.
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                Author and article information

                Journal
                Cell Microbiol
                Cell. Microbiol
                cmi
                Cellular Microbiology
                BlackWell Publishing Ltd (Oxford, UK )
                1462-5814
                1462-5822
                June 2014
                04 April 2014
                : 16
                : 6
                : 816-823
                Affiliations
                Dpt for Cell Physiology and Metabolism, Centre Medical Universitaire, University of Geneva 1 rue Michel Servet, 1211, Geneva 4, Switzerland
                Author notes
                *For correspondence. E-mail Pierre.Cosson@ 123456unige.ch ; Tel. (+41) 22 379 5294; Fax (+41) 22 379 5260.
                Article
                10.1111/cmi.12291
                4291096
                24628900
                007465d2-676e-4f32-9a9f-af912a77c272
                © 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial 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
                : 27 January 2014
                : 06 March 2014
                : 10 March 2014
                Categories
                Thematic Reviews – Alternative Host Models
                Microreview

                Microbiology & Virology
                Microbiology & Virology

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