Bacterial antigen is directly delivered to the draining lymph nodes and activates CD8+ T cells during Staphylococcus aureus skin infection.

Staphylococcus aureus is one of the most common causes of community- and hospital-acquired bacterial infection worldwide. While neutrophils play an important role in anti-S. aureus immune defense, the role of adaptive immunity is less clear. In this study, we generated a model antigen-expressing S. aureus strain to investigate the dynamics and magnitude of T cell immune responses against this pathogen. We demonstrate that S. aureus is delivered to the draining lymph nodes (LNs) by lymphatic flow immediately after intradermal inoculation. There, the bacterium initiates CD8+ cytotoxic T lymphocyte (CTL) proliferation via activating LN-resident dendritic cells. Large numbers of neutrophils are recruited to the draining LNs to engulf bacteria; however, neutrophil depletion did not impact on CTL proliferation, despite increasing bacterial burden. Tissue-resident memory T cells were formed in the skin at bacteria-inoculated sites. Yet, blood and tissue-resident memory T cells failed to prevent secondary cutaneous S. aureus infection. Our study defines the delivery kinetics of S. aureus from the skin and suggests that CTLs are dispensable for protection against skin infections.