Blog
About

7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Antigen delivery to dendritic cells shapes human CD4 + and CD8 + T cell memory responses to Staphylococcus aureus

      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.

          Abstract

          Intracellular persistence of Staphylococcus aureus favors bacterial spread and chronic infections. Here, we provide evidence for the existence of human CD4 + and CD8 + T cell memory against staphylococcal antigens. Notably, the latter could provide a missing link in our understanding of immune control of intracellular S. aureus. The analyses showed that pulsing of monocyte-derived dendritic cells (MoDC) with native staphylococcal protein antigens induced release of Th2-associated cytokines and mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) from both CD4 + and CD8 + T cells, thus revealing a state of tolerance predominantly arising from preformed memory T cells. Furthermore, G-CSF was identified as a suppressor of CD8 + T cell-derived IFNγ secretion, thus confirming a tolerogenic role of this cytokine in the regulation of T cell responses to S. aureus. Nevertheless, delivery of in vitro transcribed mRNA-encoded staphylococcal antigens triggered Th1-biased responses, e.g. IFNγ and TNF release from both naïve and memory T cells. Collectively, our data highlight the potential of mRNA-adjuvanted antigen presentation to enable inflammatory responses, thus overriding the existing Th2/Treg-biased memory T cell response to native S. aureus antigens.

          Author summary

          Staphylococcus aureus is deemed one of the most important nosocomial pathogens but, to date, there are no safe and protective vaccines. In this study we investigate the nature of the preformed T cell response to S. aureus antigens in healthy donors. Our data reveal that CD4 + and—so far not described—CD8 + T cell memory responses against native staphylococcal antigens exist but are skewed towards minimizing inflammation and promoting tolerance. The T cell response to staphylococcal antigens is characterized by the secretion of typical Th2 cytokines such as IL-5 and IL-13 and mediators associated with formation of T regulatory cells. Most importantly, G-CSF suppresses IFNγ release from pre-existent memory T cells. However, our data reveal that the use of mRNA-encoded antigens to trigger S. aureus-specific T cell responses bears the potential to override the tolerogenic bias. It favors TNF- and IFNγ-releasing T cells and may, thus, represent an innovative tool in prophylactic and therapeutic vaccine development.

          Related collections

          Most cited references 75

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

          5'-Triphosphate RNA is the ligand for RIG-I.

          The structural basis for the distinction of viral RNA from abundant self RNA in the cytoplasm of virally infected cells is largely unknown. We demonstrated that the 5'-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid-inducible protein I (RIG-I)-mediated detection of RNA molecules. Detection of 5'-triphosphate RNA is abrogated by capping of the 5'-triphosphate end or by nucleoside modification of RNA, both occurring during posttranscriptional RNA processing in eukaryotes. Genomic RNA prepared from a negative-strand RNA virus and RNA prepared from virus-infected cells (but not from noninfected cells) triggered a potent interferon-alpha response in a phosphatase-sensitive manner. 5'-triphosphate RNA directly binds to RIG-I. Thus, uncapped 5'-triphosphate RNA (now termed 3pRNA) present in viruses known to be recognized by RIG-I, but absent in viruses known to be detected by MDA-5 such as the picornaviruses, serves as the molecular signature for the detection of viral infection by RIG-I.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group.

            The consequences of infection with Staphylococcus aureus can be severe, so strategies for prevention are important. We examined S. aureus isolates from blood and from nasal specimens to determine whether the organisms in the bloodstream originated from the patient's own flora. In a multicenter study, swabs for culture were obtained from the anterior nares of 219 patients with S. aureus bacteremia. A total of 723 isolates were collected and genotyped. In a second study, 1640 S. aureus isolates from nasal swabs were collected over a period of five years and then compared with isolates from the blood of patients who subsequently had S. aureus bacteremia. In the multicenter study of S. aureus bacteremia, the blood isolates were identical to those from the anterior nares in 180 of 219 patients (82.2 percent). In the second study, 14 of 1278 patients who had nasal colonization with S. aureus subsequently had S. aureus bacteremia. In 12 of these 14 patients (86 percent), the isolates obtained from the nares were clonally identical to the isolates obtained from blood 1 day to 14 months later. A substantial proportion of cases of S. aureus bacteremia appear to be of endogenous origin since they originate from colonies in the nasal mucosa. These results provide support for strategies to prevent systemic S. aureus infections by eliminating nasal carriage of S. aureus.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Immune evasion by staphylococci.

              Staphylococcus aureus can cause superficial skin infections and, occasionally, deep-seated infections that entail spread through the blood stream. The organism expresses several factors that compromise the effectiveness of neutrophils and macrophages, the first line of defence against infection. S. aureus secretes proteins that inhibit complement activation and neutrophil chemotaxis or that lyse neutrophils, neutralizes antimicrobial defensin peptides, and its cell surface is modified to reduce their effectiveness. The organism can survive in phagosomes, express polysaccharides and proteins that inhibit opsonization by antibody and complement, and its cell wall is resistant to lysozyme. Furthermore, S. aureus expresses several types of superantigen that corrupt the normal humoral immune response, resulting in anergy and immunosuppression. In contrast, Staphylococcus epidermidis must rely primarily on cell-surface polymers and the ability to form a biolfilm to survive in the host.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Pathog
                PLoS Pathog
                plos
                plospath
                PLoS Pathogens
                Public Library of Science (San Francisco, CA USA )
                1553-7366
                1553-7374
                25 May 2017
                May 2017
                : 13
                : 5
                Affiliations
                [1 ]Division of Microbiology, Paul-Ehrlich Institute, Langen, Germany
                [2 ]Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
                [3 ]Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University Tuebingen, Auf der Morgenstelle 28/E8, Tuebingen, Germany
                Johns Hopkins School of Medicine, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                • Conceptualization: IBD JU FG MTN.

                • Data curation: JU CS MTN OT.

                • Formal analysis: JU OT.

                • Funding acquisition: IBD GB FG.

                • Investigation: IBD JU OT CS MTN AS.

                • Methodology: JU IBD GB FK FG.

                • Project administration: IBD JU.

                • Resources: IBD FG GB.

                • Supervision: IBD FG GB.

                • Validation: JU IBD.

                • Visualization: JU CS.

                • Writing – original draft: JU IBD.

                • Writing – review & editing: JU IBD FG GB CS OT MTN FK.

                Article
                PPATHOGENS-D-16-02831
                10.1371/journal.ppat.1006387
                5444865
                28542586
                © 2017 Uebele et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 6, Tables: 0, Pages: 23
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: BE3841/2-1
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: GB504/10-1
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: TRR34
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: TRR34
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: GO371/9-1
                Award Recipient :
                The work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft grant #BE3841/2-1 to IBD, #504/10-1 to GB and GO 371/9-1 and TRR34 to FG). The funding institution had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                White Blood Cells
                T Cells
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Immune Cells
                White Blood Cells
                T Cells
                Biology and Life Sciences
                Immunology
                Immune Cells
                White Blood Cells
                T Cells
                Medicine and Health Sciences
                Immunology
                Immune Cells
                White Blood Cells
                T Cells
                Biology and life sciences
                Cell biology
                Cellular types
                Animal cells
                Blood cells
                White blood cells
                T cells
                Cytotoxic T cells
                Biology and life sciences
                Cell biology
                Cellular types
                Animal cells
                Immune cells
                White blood cells
                T cells
                Cytotoxic T cells
                Biology and life sciences
                Immunology
                Immune cells
                White blood cells
                T cells
                Cytotoxic T cells
                Medicine and health sciences
                Immunology
                Immune cells
                White blood cells
                T cells
                Cytotoxic T cells
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Cytokines
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Cytokines
                Biology and Life Sciences
                Immunology
                Immune System
                Innate Immune System
                Cytokines
                Medicine and Health Sciences
                Immunology
                Immune System
                Innate Immune System
                Cytokines
                Biology and Life Sciences
                Developmental Biology
                Molecular Development
                Cytokines
                Biology and Life Sciences
                Organisms
                Bacteria
                Staphylococcus
                Staphylococcus Aureus
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Staphylococcus
                Staphylococcus Aureus
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Staphylococcus
                Staphylococcus Aureus
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Messenger RNA
                Biology and life sciences
                Cell biology
                Cellular types
                Animal cells
                Blood cells
                White blood cells
                T cells
                Memory T cells
                Biology and life sciences
                Cell biology
                Cellular types
                Animal cells
                Immune cells
                White blood cells
                T cells
                Memory T cells
                Biology and life sciences
                Immunology
                Immune cells
                White blood cells
                T cells
                Memory T cells
                Medicine and health sciences
                Immunology
                Immune cells
                White blood cells
                T cells
                Memory T cells
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Biology and Life Sciences
                Organisms
                Bacteria
                Staphylococcus
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Staphylococcus
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Staphylococcus
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology

                Comments

                Comment on this article