Immunization with a Bacterial Lipoprotein Establishes an Immuno-Protective Response with Upregulation of Effector CD4+ T Cells and Neutrophils Against Methicillin-Resistant Staphylococcus aureus Infection

Staphylococcus aureus (S. aureus) is a commensal bacterium in the human body; however, the bacterium frequently generates serious inflammation and infectious diseases. Some strains of S. aureus, such as methicillin-resistant Staphylococcus aureus (MRSA), are still a serious problem in public health facilities. Thus, an effective protection strategy is eagerly expected for the prevention and cure of MRSA infection. Here, we report that a specific fraction of an S. aureus lipoprotein (SA-LP) established a protective response against MRSA infection. The fractionated S. aureus lipoprotein SA-LP-F2, which is contained in 30-50 kDa of crude S. aureus lipoprotein (SA-LP-C), effectively activated dendritic cells (DCs) and the SA-LP-F2-pulsed DCs generated IFN-gamma+CD4+ T (Th1) and IL-17A+CD4+ T (Th17) cells by in vitro antigen presentation. The SA-LP-F2 immunization upregulated the Th1 and Th17 populations so that MRSA colonization on the skin was suppressed during the challenge phase with MRSA. By following the effector T cell upregulation, the neutrophil function, which was a substantial effector cell against MRSA, was also enhanced in the SA-LP-F2-immunized mice. Finally, we found that the protective effect of SA-LP-F2 immunization was maintained for at least 90 days because the immunized mice continued to show a protective response during the MRSA challenge period. In the MRSA challenge, reactivated Th1 and Th17 populations were maintained in the SA-LP-F2-immunized mice as compared to naive mice. In addition, the neutrophil population was also upregulated in the mice. The memory CD4+ T cell (central memory T; T-CM and effector memory T; T-EM) population was established by SA-LP-F2 immunization and was maintained at higher levels than usual. Taken together, our findings may provide a breakthrough in the establishment of an immunization strategy against MRSA infection.