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

by Suguru Saito 1,2,3,*, Su-Hui Lin 3,4 and Hui-Ya Wu 4,5,6
1
Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Kidney Research Center, Niigata University, Niigata 9518510, Japan
2
Department of Bio Medical Science, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
3
Institute of Biomedical Science, Academia Sinica, Taipei 115, Taiwan
4
Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
5
College of Health Science, Trans World University, Yunlin 640, China
6
Medical Science International, Yamagata 9980811, Japan
*
Author to whom correspondence should be addressed.
J 2019, 2(3), 326-339; https://doi.org/10.3390/j2030022
Received: 12 June 2019 / Revised: 1 August 2019 / Accepted: 1 August 2019 / Published: 8 August 2019
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. View Full-Text
Keywords: dendritic cell; S. Aureus; lipoteichoic acid; toll-like receptor; receptor cross-talking; effector T cell; acute skin inflammation dendritic cell; S. Aureus; lipoteichoic acid; toll-like receptor; receptor cross-talking; effector T cell; acute skin inflammation
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Saito, S.; Lin, S.-H.; Wu, H.-Y. The Unique Immunoregulatory Function of Staphylococcus Aureus Lipoteichoic Acid in Dendritic Cells. J 2019, 2, 326-339.

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