Microbial Exposure During Dendritic Cell Maturation Significantly Impacts Their Functional Phenotype and Activation of Autologous T Cells

We have shown that the presence of two common colonizers of the neonatal intestine, lactobacilli and Staphylococcus (S.) aureus influences immune function and/or allergy development during childhood. Further, we have demonstrated that several different Lactobacillus (L.) strains regulate S. aureus-induced immune responses in vitro. Here, we assessed how L. reuteri and S. aureus supernatants (-sn) influence the in vitro-differentiation of dendritic cells (DC), their functional characteristics and how they stimulate autologous naïve T cells in vitro. Exposure to S. aureus-sn, but not L. reuteri-sn, enhanced DC maturation of both retinoic acid (RA)-DC and conventional (CO)-DC, as shown by increased expression of CD86, HLA-DR and CD83. On the other hand, IL-6 and IL-10 production was preferentially induced by L. reuteri-sn in both CO-DC and RA-DC. DC generated in the presence of S. aureus stimulated the production of IL-2, IL-10, IL-17 and IFN-γ in naïve T cells even without further T-cell stimulation. This was not seen with DC matured in the presence of only L. reuteri. Our results show that microbial exposure during DC generation has a strong impact on subsequent T cell responses and provides support for a role of gut microbiota in early-life immune maturation.