Staphylococcus aureus Lipoprotein Induces Skin Inflammation, Accompanied with IFN-γ-Producing T Cell Accumulation through Dermal Dendritic Cells

Saito, Suguru; Quadery, Ali F.

doi:10.3390/pathogens7030064

Cited by 15 publications

(26 citation statements)

References 50 publications

(64 reference statements)

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“…Lipoprotein was isolated from S. aureus (MRSA; USA300) by following a method described in previous reports with some modifications [11,13]. Briefly, cultured S. aureus (10 7-8 CFU/mL) were harvested by centrifuging at 5000 g for 20 min.…”

Section: Lipoprotein Preparationmentioning

confidence: 99%

“…The sample was centrifuged at 12,000 g for 15 min, and then the precipitated pellet was washed with 80% ethanol and centrifuged again at 12,000 g for 5 min. The precipitated pellet was dissolved in 1 M urea/50 mM Tris-HCl and 50 mM ethylenediamine tetra acetic acid (EDTA) (pH 8.0) (crude protein extract; CPE) [11,14]. Triton X-114 was added to the protein suspension (final 1%), and then the suspension was incubated at 4 • C with gentle mixing overnight.…”

Section: Lipoprotein Preparationmentioning

confidence: 99%

“…Here, we showed that an immunization with S. aureus lipoproteins establishes effector T cells based on an adaptive immune response accompanied by the upregulation of neutrophil function against MRSA infection. The specific fraction of S. aureus lipoprotein (SA-LP-F2), which is contained in 30-50 kDa of crude S. aureus lipoprotein (SA-LP-C) [11], showed a stronger activation compared with other fractions in murine primary DCs. The SA-LP-F2 intraperitoneal (IP) injection promoted IFN-γ+CD4+ T (Th1) and IL-17A+CD4+ T (Th17) cell upregulation in an antigen-specific manner in both the spleen and lymph node (LN) as compared to the naive environment.…”

Section: Introductionmentioning

confidence: 99%

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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

Zhang

Cao

et al. 2020

Pathogens

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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.

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Section: Lipoprotein Preparationmentioning

confidence: 99%

Section: Lipoprotein Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Zhang

Cao

et al. 2020

Pathogens

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“…After being washed twice with cell culture medium, the cells were used as lymph node cells and splenocytes. Mouse bone marrow leukocytes were obtained from the tibia and femur by following a method described in a previous report [17]. After extraction of the tibia and femur, bone marrow leukocytes were flushed out with a syringe containing cell culture medium.…”

Section: Mouse Primary Cell Preparationmentioning

confidence: 99%

“…Mouse BMDCs were prepared by following a method described in a previous report [17]. At day 0, 2.0 × 10 6 of bone marrow leukocytes were suspended in 10 mL of DC culture medium (cell culture medium containing 20 ng/mL of rmGM-CSF and rmIL-4), and the cells were seeded on a 100-mm cell culture dish.…”

Section: Mouse Bone Marrow-derived Dendritic Cells (Bmdcs) Preparationmentioning

confidence: 99%

The Unique Immunoregulatory Function of Staphylococcus Aureus Lipoteichoic Acid in Dendritic Cells

Saito

Lin

2019

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Background and objectives: Lipoteichoic acid (LTA) is a structural component of Staphylococcus aureus (S. aureus) that induces severe infection disease and skin inflammation such as atopic dermatitis (AD); the biological function of LTA is still unclear. Dendritic cells (DC) are important regulators in the immune system, and the cells ectopically recognize agents that have an influence on the host immune response. We aimed to reveal the DC-based immune response against LTA to understand the novel mechanism in S. aureus related acute skin inflammation. Materials and Methods: Different doses of LTA were applied on the epidermal barrier dysfunction mice in order to evaluate the epidermal thickness, DC activation, and subsequent immunological response such as effector T-cell (Teff) activation. In addition, bone marrow-derived dendritic cells (BMDCs) were also treated with LTA, and the immunoregulatory mechanism was investigated. Results: A low dose of LTA did not induce skin inflammation at all; however, a high dose of LTA induced severe skin inflammation on epidermalba rrier dysfunction mice. Those symptoms were correlated with the DC and Teff activation status. The low-dose treatment of LTA showed a suppressive effect in pro-inflammatory cytokine production via a Toll-like receptor 2 (TLR2)-dominant manner, and the effect was significant regarding the co-treatment with another stimulatory signal such as TLR4 by lipopolysaccharide (LPS). Meanwhile, a high-dose treatment of LTA completely abolished the suppressive effect of a low-dose treatment. This phenomenon was based on C-type lectin receptors (CLRs), because the high dose of LTA greatly enhanced the expression of CLRs in the activated DCs. Conclusions: DCs sensed the dose difference of LTA, and the mechanism contributed to regulating immune responses such as effector T-cell activation, which was directly correlated with inflammatory response. This finding might provide an understanding for the novel immunological effect of LTA and S. aureus pathogenesis under inflammation, as well as the mechanism of symbiosis.J 2019, 2, 22 2 of 14 response [2,3]. Lipoteichoic acid (LTA) is released from the cell wall of gram-positive bacteria including S. aureus and induces several responses in the host [4,5]. For instance, LTA showed specific influence as a regulator of the inflammatory response [6]. LTA has been described as a ligand of Toll-like receptor 2 (TLR2), and the interaction induced the activation of signaling pathways such as the MyD88 and TRAF complexes in immune cell [7]. Finally, the signal promotes pro-inflammatory cytokine production such as TNF-α and IL-1β. However, the LTA function itself is still controversial in the host immunity. LTA induced inflammation bearing with innate immune cell accumulation on the murine skin Intradermal (ID) injection model [8]. On the other hand, naive T cells treated with LTA suppressed the differentiation into effector T cells by immunological tolerance [9]. Thus, the exact biological and immunological function of LTA is still...

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The role of Staphylococcus aureus lipoproteins in hematogenous septic arthritis

Mohammad

Ali

et al. 2020

Sci Rep

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permanent joint dysfunction is a devastating complication in patients with septic arthritis. Staphylococcus aureus (S. aureus) lipoproteins (Lpp), the predominant ligands for TLR2, are known to be arthritogenic and induce bone destruction when introduced directly into the joint. Here, we aim to investigate the importance of S. aureus Lpp and TLR2 in a hematogenous septic arthritis model, which is the most common route of infection in humans. C57BL/6 wild-type and TLR2 deficient mice were intravenously inoculated with S. aureus Newman parental strain or its lipoprotein-deficient Δlgt mutant strain. the clinical course of septic arthritis, radiological changes, and serum levels of cytokines and chemokines, were assessed. newman strain induced more severe and frequent clinical septic polyarthritis compared to its Δlgt mutant in TLR2 deficient mice, but not in wild-type controls. Bone destruction, however, did not differ between groups. Lpp expression was associated with higher mortality, weight loss as well as impaired bacterial clearance in mouse kidneys independent of TLR2. Furthermore, Lpp expression induced increased systemic pro-inflammatory cytokine and neutrophil chemokine release. Staphylococcal Lpp are potent virulence factors in S. aureus systemic infection independent of host TLR2 signalling. However, they have a limited impact on bone erosion in hematogenous staphylococcal septic arthritis. Septic arthritis remains a devastating and invasive joint disease. Due to its rapidly progressing nature, septic arthritis is considered a medical emergency 1 with a poor prognosis. Despite advances in understanding and treatment of infectious diseases, the prospect of patients with septic arthritis has remained poor. Almost half of the patients will suffer from permanent joint destruction 2 , if treatment is not initiated immediately 3. The estimated incidence of septic arthritis in the general population is approximately 6-10 cases per 100,000 individuals per year 4. However, in patients with an underlying joint disease, such as rheumatoid arthritis (RA), the incidence of septic arthritis is nearly 10 times higher than in the general population 4. Septic arthritis is most often caused by Staphylococcus aureus (S. aureus), a pathogenic Gram-positive bacterium 5. S. aureus-induced septic arthritis has been extensively studied for the past few decades; several virulence factors as well as various host-factors targeted by the bacterium have been identified 6-11. However, much still remains elusive regarding the bacteria-host interaction in S. aureus septic arthritis. Staphylococcal lipoproteins (Lpp), important bacterial molecules in S. aureus, consist of a lipid-moiety and a protein-part, and are anchored in the bacterial cytoplasmic membrane 12. Lpp are important for bacterial survival during infection due to their role in maintaining the metabolic activity of the bacteria 13,14. The lipid structure of Lpp is known to stimulate the innate immune system through activation of pattern recognition receptors 15 , and bacte...

show abstract

Staphylococcus aureus Lipoprotein Induces Skin Inflammation, Accompanied with IFN-γ-Producing T Cell Accumulation through Dermal Dendritic Cells

Cited by 15 publications

References 50 publications

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

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

The Unique Immunoregulatory Function of Staphylococcus Aureus Lipoteichoic Acid in Dendritic Cells

The role of Staphylococcus aureus lipoproteins in hematogenous septic arthritis

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