gms | German Medical Science

Staphylococcus aureus colonizes the human mucosa, which serves as a reservoir for nosocomial infections caused by this pathogen [1]. To date, the immune response and the T cell response in particular to S. aureus remains poorly defined [2]. Here, we present a novel mRNA-based approach for the characterization of staphylococcal antigen-specific human T cell responses and provide evidence for the existence of human CD4+ and CD8+ T cell memory against this pathogen.

Human monocyte-derived dendritic cells (MoDC) were loaded with in vitro transcribed (ivT) mRNA encoding one of the most important virulence factors protein A (spa), a major Toll-like receptor (TLR) 2 ligand SitC (sitC), or an accessory genetic element PBP2a (mecA) mediating resistance against beta-lactam antibiotics. Co-incubation of MoDC with autologous CD8+ T cells induced strong IFN-gamma production. In contrast, stimulation of MoDC with the corresponding protein antigens SpA, SitC and PBP2a revealed only low IFNγ secretion suggesting that the mRNA’s adjuvant effect is necessary to trigger IFNγ secretion in S. aureus-specific T cells.

Moreover, mRNA-encoded antigens elicited a strong Th1-biased immune response characterized by production of pro-inflammatory IFNγ and TNF in both naïve and memory T cells. In contrast, stimulation with the corresponding proteins induced low levels of Th2-associated cytokines, as well as mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) predominantly in memory T cells.

Altogether, our data highlight the potential of mRNA-adjuvanted antigen presentation to enable inflammatory responses, thus (re)-polarizing the existing Th2/Treg-biased memory T cell response to native S. aureus antigens [3].