Antigen delivery to dendritic cells shapes human CD4<sup>+</sup> and CD8<sup>+</sup> T cell memory responses to <i>Staphylococcus aureus</i>
by Julia Uebele, Christoph Stein, Minh-Thu Nguyen, Anja Schneider, Franziska Kleinert, Olga Tichá, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding
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.Publisher URL: http://journals.plos.org/plosone/article
DOI: 10.1371/journal.ppat.1006387
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