6). As shown, Listerianeg CD8α+ DCs up- (or down-) regulated the distinct maturation markers with a 1.5- to a 2.5-fold difference between mice that received a protective and a non-protective dose of secA2−Lm. In agreement with our hypothesis, Listeriapos CD8α+ DCs purified from protected animals also exhibited a stronger modulation of their maturation markers (∼two-fold)

than those from non-protected mice. In correlation with this result, cell-surface expression levels of CD86, CD80 and CD40 costimulatory molecules on infected GFP+ CD8α+ cDC KU-57788 manufacturer only but not on the non-infected cDC (CD8α+ or CD8α−) was 2–3 times stronger (Supporting Information Fig. 6). Therefore, in addition to receiving signals from bacteria replicating inside their cytosol, CD8α+ DCs from protected mice integrated additional buy R428 signals – likely from the stronger inflammatory environment – which accounted for

the observed difference of maturation with non-protected mice. We have investigated the ability of the two splenic cDC subsets to induce antibacterial memory CD8+ T cells that can protect against a recall infection. We found that CD8α+ cDCs from primary immunized hosts are the most efficient cDC subtype for transferring long-term, anti-Lm memory CD8+ T-cell-mediated protection to naïve recipient animals. Since both DCs subsets were loaded with saturating amounts of the same antigenic peptide and expressed equivalent cell-surface levels of MHC class I molecules, such features are independent of their capacity to process MHC class AZD9291 datasheet I-associated antigens. Interestingly, CD8α+ cDCs become endowed with these functional features as early as 5 h following the primary immunization and this requires cytosolic signals that are potentiated by extracellular inflammatory signals delivered by bacterial infection of the host. Several

seminal studies established that cDCs are key players to prime naïve antigen-specific CD8+ T cells in vivo 3, 4. While these reports support a critical function for splenic CD8α cDCs in initiating primary CD8+ T-cell responses in vivo 3, 4, 9, 11, 12, 14, 27–30, none of them had addressed the question of their ability to set memory development, i.e. whether – and to which extent – they exhibit the functional capacity to induce antibacterial protective CD8 memory. By showing that splenic CD8α cDCs become rapidly conditioned to induce anti-Lm protective memory CD8+ T cells and are best to provide such effect in vivo, we highlight a novel feature of these cells. In addition, we uncouple this functional property of CD8α+ cDCs from their ability to process the antigens from the bacteria.