How do splenic CD8α+ cDCs become able to imprint the functional characteristics of memory cells? DCs can sense the environment by expressing find protocol intra- and extracellular PRRs 5. During Lm infection, bacterial escape to host cell cytosol and SecA2-dependent cytosolic signaling are both necessary to induce memory CD8+ T-cell-mediated protective immunity 16–18, 20. Here, we further suggest that these signals likely converge to a specific subset of spleen cDCs, the CD8α+ cDCs, that then is sufficient to deliver
all information to naïve CD8+ T cells. We also show that direct microbial-derived signals from inside their cytosol are required for this phenomenon. This is in contrast to the LCMV infection model that involves cross-priming by CD8α+ DCs as direct infection of DCs prevents their capacity to initiate the cytotoxic T-cell response 37. Thus, splenic CD8α+ DCs licensing by an intracellular bacteria and a non-cytolytic virus arose from distinct mechanisms. Since the number of live Lm per infected CD8α+ cDCs is identical in protected and non-protected animals, cytosolically delivered signals are likely similar on a per
cell basis. However, immunizing recipient mice this website with the exact same numbers of infected CD8α+ cDCs purified from both conditions of immunization demonstrated that only cells from protected mice induced protective memory, suggesting that CD8α+ cDCs from protected mice receive distinct extracellular Enzalutamide order signals that likely play a critical role in optimizing their functional features, independently of the level and duration of presented antigenic peptides (DC were pulsed with exogenous peptide before
transfer). In fact, we observed a better maturation profile of CD8α+ cDCs and a much stronger inflammatory environment in the spleen of mice immunized with the protective dose of secA2−Lm. Since most Listeria+ spleen cells are phagocytes, they may be the cells that provide such extracellular signals to infected CD8α+ cDCs 38, 39. Of note, the chemokines/cytokines detected within this early splenic inflammatory environment of protected animals are also involved in DCs maturation 39–41. Previous reports showed that CD4+ T cells optimally differentiate into Th1 effector and memory cells only when primed by DCs that have received direct microbial-derived danger signals 38, 39, 42. Indirect release of inflammatory mediators only or lack of inflammation on PAMP-activated DCs failed to support such differentiation. Here we found that two levels of bacterial signals (i) from inside the cytosol and (ii) from the extracellular microbial-derived inflammation need to be delivered to the priming APC to promote pathogen-specific memory CD8+ T-cell differentiation.