ABSTRACTStaphylococcus aureusis a human pathogen responsible for high morbidity and mortality worldwide. Recurrent infections with this bacterium are common, suggesting thatS. aureusthwarts the development of sterilizing immunity.S. aureusstrains that cause disease in humans produce up to five different bicomponent toxins (leukocidins) that target and lyse neutrophils, innate immune cells that represent the first line of defense againstS. aureusinfections. However, little is known about the role of leukocidins in blunting adaptive immunity. Here, we explored the effects of leukocidins on human dendritic cells (DCs), antigen-presenting cells required for the development of adaptive immunity. Using anex vivoinfection model of primary human monocyte-derived dendritic cells, we found thatS. aureus, including strains from different clonal complexes and drug resistance profiles, effectively kills DCs despite efficient phagocytosis. Although all purified leukocidins could kill DCs, infections with live bacteria revealed thatS. aureustargets and kills DCs primarily via the activity of leukocidin LukAB. Moreover, using coculture experiments performed with DCs and autologous CD4+T lymphocytes, we found that LukAB inhibits DC-mediated activation and proliferation of primary human T cells. Taken together, the data determined in the study reveal a novel immunosuppressive strategy ofS. aureuswhereby the bacterium blunts the development of adaptive immunity via LukAB-mediated injury of DCs.IMPORTANCEAntigen-presenting cells such as dendritic cells (DCs) fulfill an indispensable role in the development of adaptive immunity by producing proinflammatory cytokines and presenting microbial antigens to lymphocytes to trigger a faster, specific, and long-lasting immune response. Here, we studied the effect ofStaphylococcus aureustoxins on human DCs. We discovered that the leukocidin LukAB hinders the development of adaptive immunity by targeting human DCs. The ability ofS. aureusto blunt the function of DCs could help explain the high frequency of recurrentS. aureusinfections. Taken together, the results from this study suggest that therapeutically targeting theS. aureusleukocidins may boost effective innate and adaptive immune responses by protecting innate leukocytes, enabling proper antigen presentation and T cell activation.
Lymphocyte Transformation Test Effectivity based on the Antigen presenting Cells Employed in Immediate Allergic Reactions to Betalactams
