Lactobacillus reuteri and staphylococcus aureus differentially influence the generation of monocyte-derived dendritic cells and subsequent autologous T cell responses

Abstract

Introduction: In early-life, the immature mucosal barrier allows contact between the gut microbiota and the developing immune system. Due to their strategic location and their ability to sample luminal antigen, dendritic cells (DC) play a central role in the interaction of microbes and immune cells in the gut. Here, we investigated how two bacteria associated with opposite immune profiles in children, that is, Lactobacillus (L.) reuteri and Staphylococcus (S.) aureus, influenced the differentiation of monocytes in vitro as well how the generated DC impacted T cell responses. Methods: We exposed monocyte cultures to cell-free supernatants (CFS) from these bacteria during their differentiation to DC. Results: The presence of L. reuteri-CFS during DC differentiation resulted in DC with a more mature phenotype, in terms of up-regulated surface markers (HLADR, CD86, CD83, CCR7) and enhanced cytokine production (IL6, IL10, and IL23), but had a reduced phagocytic capacity compared with non-treated monocytederived DC (Mo-DC). However, upon LPS activation, L. reuteri-CFS-generated DC displayed a more regulated phenotype than control Mo-DC with notable reduction of cytokine responses both at mRNA and protein levels. In contrast, S. aureus-CFS-generated DC were more similar to control Mo-DC both without and after LPS stimulation, but they were still able to induce responses in autologous T cells, in the absence of further T cell stimulation. Conclusions: We show that bacterial signals during DC differentiation have a profound impact on DC function and possibly also for shaping the T cell pool.