title: 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.affiliation: Department of Dermatology, H.B. Wells Center for Pedoatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Zhang
authors.forename: Nico
authors.initials: N
authors.lastname: Mousdicas
authors.forename: Qiaofang
authors.initials: Q
authors.lastname: Yi
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Hassani
authors.forename: Steven D
authors.initials: SD
authors.lastname: Billings
authors.forename: Susan M
authors.initials: SM
authors.lastname: Perkins
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Howard
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishii
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Travers
mesh_terms: D000818:Animals; D002118:Calcium / Q000276:immunology; D002460:Cell Line; D003876:Dermatitis, Atopic / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000276:immunology* / Q000473:pathology; D004357:Drug Synergism; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010980:Platelet Membrane Glycoproteins / Q000819:agonists* / Q000172:deficiency / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000172:deficiency / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013203:Staphylococcal Infections / Q000276:immunology / Q000473:pathology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000276:immunology; D013682:Teichoic Acids / Q000008:administration & dosage* / Q000737:chemistry; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D013682:Teichoic Acids; C039351:platelet activating factor receptor; D016753:Interleukin-10; C009900:lipoteichoic acid; C083283:1-O-hexadecyl-2-N-methylcarbamol -sn-glycerol-3-phosphocholine; D004139:Dinitrofluorobenzene; D002118:Calcium