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About the Authors:
Julia Uebele
Affiliations Division of Microbiology, Paul-Ehrlich Institute, Langen, Germany, Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
Christoph Stein
Affiliations Division of Microbiology, Paul-Ehrlich Institute, Langen, Germany, Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
Minh-Thu Nguyen
Affiliation: Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University Tuebingen, Auf der Morgenstelle 28/E8, Tuebingen, Germany
Anja Schneider
Affiliation: Division of Microbiology, Paul-Ehrlich Institute, Langen, Germany
Franziska Kleinert
Affiliation: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
Olga Tichá
Affiliation: Division of Microbiology, Paul-Ehrlich Institute, Langen, Germany
Gabriele Bierbaum
Affiliation: Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
Friedrich Götz
Affiliation: Interfaculty Institute of Microbiology and Infection Medicine (IMIT), University Tuebingen, Auf der Morgenstelle 28/E8, Tuebingen, Germany
Isabelle Bekeredjian-Ding
* E-mail: [email protected]
Affiliations Division of Microbiology, Paul-Ehrlich Institute, Langen, Germany, Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Bonn, Germany
ORCID http://orcid.org/0000-0001-6646-5888Abstract
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 IFN[gamma] 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. IFN[gamma] 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...