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

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.