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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Research Article Immunology

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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Figure 2

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Effect of intradermal injections of CPAF, LTA, or PDG on skin inflammati...
Effect of intradermal injections of CPAF, LTA, or PDG on skin inflammation. The dorsal sides of ears of wild-type and PAF-R–/– mice were injected with 100 ng CPAF, 10 μg LTA, 10 μg PDG (wild-type mice only), or 2.0 mg histamine in 1 ear and BSA vehicle control on the other. After 2 hours, 5-mm punch biopsies were performed and tissues weighed, and the differences in ear biopsy specimen weights between CPAF/LTA versus BSA vehicle assessed. (A) Intradermal injection of CPAF or LTA induced local cutaneous inflammation (as measured by increased tissue weight) in wild-type but not PAF-R–/– mice. The data consist of the mean ± SD of the difference between LTA/PDG/CPAF/histamine and vehicle-injected ear biopsy specimen weights using 6–7 mice in each group. *Statistically significant (P < 0.05) difference in ear thickness between WT and PAF-R–/– mice. (B) Representative H&E-stained sections from CPAF-, LTA-, histamine-, or vehicle control–injected ear biopsy specimens revealed significant edema with scattered neutrophils and a few eosinophils in the skin of wild-type mice after intradermal injection of CPAF or LTA compared with essentially no effect on the ear skin of PAF-R–/– mice. Both wild-type and PAF-R–/– mice were equally responsive to intradermal injection of histamine as positive control. CON, control. Magnification, ×100.