Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2018

Targeting the middle man: Staphylococcus aureus targets human dendritic cells thereby hindering the activation of effector T lymphocytes (#9)

Victor Torres 1
  1. NYU School of Medicine, New York, NEW YORK, United States

Staphylococcus aureus is a human pathogen responsible for high morbidity and mortality worldwide. Recurrent infections with this bacterium are common, suggesting that S. aureus thwarts the development of sterilizing immunity. Strains that cause disease in humans produce an array of bi-component, pore-forming toxins, commonly known as leukocidins, that target and injure immune cells. However, the contribution of these toxins to the observed impairment of adaptive immunity towards S. aureus is not fully understood. Dendritic cells (DCs) are professional antigen-presenting cells required for the training and development of adaptive immunity. I will discuss our recent findings on the effects of leukocidins on human DCs. By taking advantage of an ex vivo infection model of primary human monocyte-derived dendritic cells, we found that S. aureus, including strains from different lineages and drug resistance profiles, efficiently targets and kills human DCs. We observed that although S. aureus is taken up readily by DCs, the bacteria are nevertheless very potent at killing these cells. Infections with live bacteria lacking each of the individual toxins revealed that S. aureus-mediated killing of DCs is driven by a single leukocidin known as LukAB. Experiments using co-culture experiments with DCs, S. aureus, and autologous CD4+ T lymphocytes further unraveled that by targeting human DCs, LukAB inhibits DC-mediated activation and proliferation of primary human T cells. Altogether, these findings reveal a novel immunosuppressive strategy of S. aureus, whereby the bacterium can blunt the development of adaptive immunity via LukAB-mediated injury of DCs.