Staphylococcus aureus causes severe disease with multiple tissue tropisms. Clinical data suggests that chronic and recurrent disease occurs exclusively in skin and soft tissue sites. Yet, immunity to pathogens can be induced in the skin. This implies that induction of protective, adaptive immunity is critically dependent on the tissue site of initial infection. Furthermore, S. aureus may utilize tissue-specific mechanisms to suppress the development of protective immunity. How immunity to S. aureus is induced is poorly understood due to the lack of tractable, in vivo antigen-specific models to which S. aureus-specific adaptive immunity can be analyzed. Therefore, we generated a novel chicken egg ovalbumin (OVA) secreting S. aureus strain to follow OVA-specific CD4+ T cells in recipient murine hosts. Here, we demonstrate that bacteremia induces protection against secondary skin challenge dermonecrosis and control of pathogen load. Bacteremia induced Th1 OT-II subset differentiation, generating memory cells which responded to skin re-challenge. Conversely, skin infection offered no detectable protection against secondary challenge, and failed to induce both canonical T helper cytokines and responsive, long-lasting memory cells among donor OT-IIs. Loss of Hla expression by S. aureus resulted in the rescue of OT-II Th1 responses after skin infection and enhanced memory cell induction. Intradermal S. aureus infection resulted in the loss of CD11b+ dermal dendritic cells and Langerhans cells in the skin and reduced both migration and accumulation of DCs to the skin draining lymph node. Infection with LAC hla::erm mutant strain restored DC accumulation in both the skin draining lymph nodes and the skin site. Immune sera protected DC loss in naïve animals during S. aureus skin infection. Furthermore, active immunization against inactive mutant of HlaH35L protected DC populations in the skin and draining lymph nodes after S. aureus infection. Taken together, these data implicate Hla as a novel suppressor of antigen-specific CD4+ T cell priming and long-lasting memory formation against S. aureus. We hypothesize that DC targeting by Hla prevents efficient priming of OT-II memory and cytokine responses. We propose that successful vaccination trials should target pediatric populations, as they likely have functional S. aureus-specific CD4 T cells, and immunize against Hla to protect DCs at barrier sites frequently breached by S. aureus. Such strategies will convert normally immunosuppressive encounters with S. aureus into immune boosting events.