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
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 115 Issue 10 Pg. 2855-61 (Oct 2005) ISSN: 0021-9738 [Print] United States
• PMID: 16184199 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Lipopolysaccharides
• Platelet Activating Factor
• Platelet Membrane Glycoproteins
• Receptors, G-Protein-Coupled
• Teichoic Acids
• platelet activating factor receptor
• Interleukin-10
• lipoteichoic acid
• 1-O-hexadecyl-2-N-methylcarbamol -sn-glycerol-3-phosphocholine
• Dinitrofluorobenzene
• Calcium

Topics

• Animals
• Calcium (immunology)
• Cell Line
• Dermatitis, Atopic (immunology, microbiology, pathology)
• Dinitrofluorobenzene (adverse effects)
• Drug Hypersensitivity (immunology, pathology)
• Drug Synergism
• Humans
• Hypersensitivity, Delayed (chemically induced, immunology, pathology)
• Inflammation (chemically induced, immunology, pathology)
• Interleukin-10 (immunology)
• Lipopolysaccharides (administration & dosage, chemistry)
• Mice
• Mice, Knockout
• Platelet Activating Factor (administration & dosage, analogs & derivatives)
• Platelet Membrane Glycoproteins (agonists, deficiency, immunology)
• Receptors, G-Protein-Coupled (agonists, deficiency, immunology)
• Skin (immunology, pathology)
• Staphylococcal Infections (immunology, pathology)
• Staphylococcus aureus (chemistry, immunology)
• Teichoic Acids (administration & dosage, chemistry)
• Th1 Cells (immunology, pathology)
• Th2 Cells (immunology, pathology)