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

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. © 2017 uebele et al.