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

Abstract

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-γ+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; TCM and effector memory T; TEM) 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.

Creatine supplementation enhances immunological function of neutrophils by increasing cellular adenosine triphosphate

“…1D ). ROS production, which is an antibacterial response, was also measured in the neutrophils [ 31 ]. Under the basal and LPS-stimulated conditions, ROS production was significantly increased in the creatine-treated neutrophils as compared with the vehicle controls ( Fig.…”

Lymphocyte antigen 6 complex locus G6D downregulation is a novel parameter for functional impairment of neutrophils in aged mice

“…Therefore, we decided to focus on the neutrophil’s function in aged mice. To clarify the age-associated functional change of neutrophils, we assessed some parameters related with antibacterial immunity by in vitro functional assays ( 7 , 18 , 19 ).…”

“…The neutrophils were isolated from the bone marrow (BM) by the following protocol described in the previous reports ( 17 , 18 ). Briefly, the BM cells were flushed out from the tibia and femur in RPMI complete medium (RPMI 1640 supplemented with 10% fetal bovine serum (FBS), penicillin 100 U/ml, streptomycin 100 U/ml) using a 10-ml syringe with a 27G needle.…”

“…The frozen stock was thawed on ice, and the bacteria were cultured in LB medium following the product manual. The bacterial colony-forming unit (CFU/mL) was calculated by following the previous reports ( 17 , 18 ).…”

Bacterial Lipoteichoic Acid Attenuates Toll-Like Receptor Dependent Dendritic Cells Activation and Inflammatory Response

“…The strainer was washed with cell culture medium, then all flow through was passed through a 5 mL syringe with a 22 G needle to make single cell suspension. Mouse bone marrow leukocytes were obtained from the tibia and femur by following a method described in a previous report [ 28 ]. Briefly, the cells were flushed out from the tibia and femur by a 10 mL syringe with a 27 G needle containing cell culture medium.…”