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      Plasmacytoid Dendritic Cells: Neglected Regulators of the Immune Response to Staphylococcus aureus

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          Abstract

          Plasmacytoid dendritic cells (pDC) are a rare subset of leukocytes equipped with Fcγ and Fcε receptors, which exert contrary effects on sensing of microbial nucleic acids by endosomal Toll-like receptors. In this article, we explain how pDC contribute to the immune response to Staphylococcus aureus. Under normal circumstances the pDC participates in the memory response to the pathogen: pDC activation is initiated by uptake of staphylococcal immune complexes with IgG or IgE. However, protein A-expressing S. aureus strains additionally trigger pDC activation in the absence of immunoglobulin. In this context, staphylococci exploit the pDC to induce antigen-independent differentiation of IL-10 producing plasmablasts, an elegant means to propagate immune evasion. We further discuss the role of type I interferons in infection with S. aureus and the implications of these findings for the development of immune based therapies and vaccination.

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          Most cited references125

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          Plasmacytoid dendritic cells in immunity.

          Human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts of type I interferons in response to viruses, the so-called natural interferon-producing cells. As a result, intensive investigation is now focused on the potential functions of plasmacytoid dendritic cells in both innate and adaptive immunity. Here we review recent progress on the characterization of plasmacytoid dendritic cell origin, development, migration and function in immunity and tolerance, as well as their effect on human diseases.
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            Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus.

            Dendritic cells (DCs) are important in regulating both immunity and tolerance. Hence, we hypothesized that systemic lupus erythematosus (SLE), an autoimmune disease characterized by autoreactive B and T cells, may be caused by alterations in the functions of DCs. Consistent with this, monocytes from SLE patients' blood were found to function as antigen-presenting cells, in vitro. Furthermore, serum from SLE patients induced normal monocytes to differentiate into DCs. These DCs could capture antigens from dying cells and present them to CD4-positive T cells. The capacity of SLE patients' serum to induce DC differentiation correlated with disease activity and depended on the actions of interferon-alpha (IFN-alpha). Thus, unabated induction of DCs by IFN-alpha may drive the autoimmune response in SLE.
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              Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology.

              We show here that mouse interferon-alpha (IFN-alpha)-producing cells (mIPCs) are a unique subset of immature antigen-presenting cells (APCs) that secrete IFN-alpha upon stimulation with viruses. mIPCs have a plasmacytoid morphology, can be stained with an antibody to Ly6G and Ly6C (anti-Ly6G/C) and are Ly6C+B220+CD11cloCD4+; unlike other dendritic cell subsets, however, they do not express CD8alpha or CD11b. Although mIPCs undergo apoptosis in vitro, stimulation with viruses, IFN-alpha or CpG oligonucleotides enhanced their survival and T cell stimulatory activity. In vivo, mIPCs were the main producers of IFN-alpha in cytomegalovirus-infected mice, as depletion of Ly6G+/C+ cells abrogated IFN-alpha production. mIPCs produced interleukin 12 (IL-12) in response to viruses and CpG oligodeoxynucleotides, but not bacterial products. Although different pathogens can selectively engage various APC subsets for IL-12 production, IFN-alpha production is restricted to mIPCs' response to viral infection.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/28149
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                23 May 2014
                2014
                : 5
                : 238
                Affiliations
                [1] 1Institute for Microbiology, Immunology and Parasitology, University Hospital Bonn , Bonn, Germany
                [2] 2Department of Pediatrics, University Hospital Heidelberg , Heidelberg, Germany
                [3] 3Department of Infectious Diseases, Medical Microbiology and Hygiene, University Hospital Heidelberg , Heidelberg, Germany
                Author notes

                Edited by: Fabio Bagnoli, Novartis Vaccines, Italy

                Reviewed by: Eliana Marina Coccia, Istituto Superiore di Sanità, Italy; Elisabetta Adelaide Pia Soldaini, Novartis Vaccines, Italy

                *Correspondence: Isabelle Bekeredjian-Ding, Institute for Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany e-mail: bekeredjian-ding@ 123456uni-bonn.de

                This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology.

                Article
                10.3389/fimmu.2014.00238
                4033153
                24904586
                195434a4-7d59-4513-bcc4-b470d55ce7bb
                Copyright © 2014 Bekeredjian-Ding, Greil, Ammann and Parcina.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 February 2014
                : 08 May 2014
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 148, Pages: 10, Words: 8615
                Categories
                Immunology
                Perspective Article

                Immunology
                pdc,staphylococcus aureus,type i interferons,immune complexes,bacteria,tolerance,autoimmunity,allergy

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