Staphylococcus aureus activates dendrite elongation in dendritic cells.

Dendritic cells (DCs) are thought to extend dendrites to enhance the efficiency of antigen uptake and presentation. We previously reported that short-chain fatty acids (SCFAs), such as butyrate and valerate, promote dendrite extension in DCs. In this study, we found that the human pathogen Staphylococcus aureus also induces dendrite extension in DCs and investigated the underlying mechanisms. Dendrite extension in DC2.4 cells was induced not only by live S. aureus but also by heat-killed bacteria and purified peptidoglycan (PGN). DC2.4 cells lacking TLR2 or its adaptor protein MyD88 extend dendrites in response to SCFAs, but failed to extend dendrites in response to S. aureus. Furthermore, inhibitors of ERK, PI3K, and Cdc42 suppressed dendrite extension triggered by S. aureus. Co-stimulation with S. aureus and butyrate enhanced dendrite extension beyond either stimulus alone. DC2.4 cells co-stimulated with S. aureus and butyrate also showed increased uptake of insoluble beads and, upon co-culture with T cells, induced elevated production of IL-17 and IL-10 by T cells. Collectively, these findings suggest that S. aureus activates ERK/PI3K/Cdc42 signaling through TLR2 recognition of PGN to drive dendrite extension in DCs. In addition, S. aureus promotes dendrite extension in DCs via a pathway distinct from that of SCFAs, thereby acting cooperatively with SCFAs to enhance immune responses.