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

Autor: Olga Ticha, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding, Julia Uebele, Franziska Kleinert, Minh-Thu Nguyen, Anja Schneider, Christoph Stein
Jazyk: angličtina
Rok vydání: 2017
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Physiology
Staphylococcus
CD8-Positive T-Lymphocytes
Pathology and Laboratory Medicine
T-Lymphocytes
Regulatory
Biochemistry
Memory T cells
White Blood Cells
Interleukin 21
0302 clinical medicine
Animal Cells
Immune Physiology
Granulocyte Colony-Stimulating Factor
Medicine and Health Sciences
Cytotoxic T cell
Staphylococcus Aureus
IL-2 receptor
Enzyme-Linked Immunoassays
lcsh:QH301-705.5
Antigen Presentation
Innate Immune System
T Cells
Messenger RNA
Staphylococcal Infections
Natural killer T cell
Interleukin-10
Bacterial Pathogens
Nucleic acids
medicine.anatomical_structure
Medical Microbiology
Cytokines
Cellular Types
Pathogens
Research Article
lcsh:Immunologic diseases. Allergy
Immune Cells
T cell
Immunology
Antigen presentation
Cytotoxic T cells
Biology
Research and Analysis Methods
Microbiology
03 medical and health sciences
Th2 Cells
Virology
Immune Tolerance
Genetics
medicine
Humans
Immunoassays
Antigen-presenting cell
Microbial Pathogens
Molecular Biology
Antigens
Bacterial
Blood Cells
Bacteria
Organisms
Biology and Life Sciences
Dendritic Cells
Cell Biology
Molecular Development
030104 developmental biology
lcsh:Biology (General)
Immune System
Immunologic Techniques
Interleukin-2
RNA
Parasitology
lcsh:RC581-607
Memory T cell
Developmental Biology
030215 immunology
Zdroj: PLoS Pathogens, Vol 13, Iss 5, p e1006387 (2017)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: 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.
Databáze: OpenAIRE
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