Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor
Qiwei Zhang, … , Takao Shimizu, Jeffrey B. Travers
Qiwei Zhang, … , Takao Shimizu, Jeffrey B. Travers
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2855-2861. https://doi.org/10.1172/JCI25429.
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Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor

Abstract

Staphylococcus aureus infections are known triggers for skin inflammation and can modulate immune responses. The present studies used model systems consisting of platelet-activating factor receptor–positive and –negative (PAF-R–positive and –negative) cells and PAF-R–deficient mice to demonstrate that staphylococcal lipoteichoic acid (LTA), a constituent of Gram-positive bacteria cell walls, acts as a PAF-R agonist. We show that LTA stimulates an immediate intracellular Ca2+ flux only in PAF-R–positive cells. Intradermal injections of LTA and the PAF-R agonist 1-hexadecyl-2-N-methylcarbamoyl glycerophosphocholine (CPAF) induced cutaneous inflammation in wild-type but not PAF-R–deficient mice. Systemic exposure to LTA or CPAF inhibited delayed-type hypersensitivity (DTH) reactions to the chemical dinitrofluorobenzene only in PAF-R–expressing mice. The inhibition of DTH reactions was abrogated by the addition of neutralizing antibodies to IL-10. Finally, we measured levels of LTA that were adequate to stimulate PAF-R in vitro on the skin of subjects with infected atopic dermatitis. Based on these studies, we propose that LTA exerts immunomodulatory effects via the PAF-R through production of the Th2 cytokine IL-10. These findings show a novel mechanism by which staphylococcal infections can inhibit Th1 reactions and thus worsen Th2 skin diseases, such as atopic dermatitis.

Authors

Qiwei Zhang, Nico Mousdicas, Qiaofang Yi, Mohammed Al-Hassani, Steven D. Billings, Susan M. Perkins, Katherine M. Howard, Satoshi Ishii, Takao Shimizu, Jeffrey B. Travers

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Effects of CPAF and LTA on topical DTH reactions in wild-type versus PAF...
Effects of CPAF and LTA on topical DTH reactions in wild-type versus PAF-R–/– mice. (A) Effect of CPAF/LTA on DTH sensitization reactions. 250 ng CPAF or 100 μg LTA was injected i.p. into wild-type or PAF-R–/– mice. As described in Methods, the mice underwent sensitization to topical DNFB 5 days later, and 10 days later reactions were elicited by painting DNFB or vehicle on ears. Punch biopsies were performed 24 hours later, and the differences between biopsy specimen weights of DNFB- and vehicle-treated ears were measured using 6–8 mice in each group. (B) Effects of CPAF and LTA on DTH elicitation reactions. In these experiments, the mice were first sensitized to topical DNFB. Nine days after immunization, 250 ng CPAF or 100 μg LTA was injected i.p.; 1 day after injection, DTH reactions were elicited by painting DNFB or vehicle control on ears. Punch biopsies were performed 24 hours later, and the differences between biopsy specimen weights of DNFB- and vehicle-treated ears were measured using 7–8 mice in each group. *Statistically significant (P < 0.05) decrease in difference of ear biopsy specimen weights of CPAF- or LTA-treated PAF-R–/– mice in comparison with wild-type mice.