title: The elicitation step of nickel allergy is promoted in mice by microbe-related substances, including some from oral bacteria.
abstract: Microbial components activate the host's innate immunity via interactions with molecules including TLRs and NODs. We previously reported that in mice (i) Escherichia coli lipopolysaccharide (LPS; TLR4 agonist) promotes Ni-allergy even in T-cell-deficient mice, (ii) E. coli LPS reduces the minimum allergy-inducing concentrations of Ni at both the sensitization and elicitation steps, and (iii) various microbe-related substances promote sensitization to Ni. Here, we examined the effects of microbe-related substances at the elicitation step. Mice (except for TLR4-mutated C3H/HeJ mice) were sensitized to Ni by intraperitoneal injection of NiCl(2) + E. coli LPS. Ten days later their ear-pinnas were challenged with 1 μM NiCl(2) with or without a test substance. Although NiCl(2) alone at this concentration does not induce Ni-allergy, its combination with the following substances induced Ni-allergy in BALB/c mice: LPS preparations from oral gram-negative bacteria (Prevotella intermedia and Porphyromonas gingivalis), a mannan preparation from a fungus (Saccharomyces cerevisiae), and synthetic NOD2 and TLR2 agonists. The effect of the mannan preparation was small in C3H/HeJ mice (sensitized with NiCl(2) + the P. intermedia preparation). The P. intermedia preparation promoted Ni-allergy in C3H/HeJ and nude mice, but not in mice deficient in either TLR2 or histidine decarboxylase. Intragingival injection of the P. intermedia preparation and later challenge with NiCl(2) alone to ear-pinnas also promoted Ni-allergy. These results indicate that (i) in Ni-allergy, a microbial milieu or innate immunity is important at the elicitation step, too, and (ii) some oral bacteria may promote Ni-allergy via TLR2-stimulant(s) production.
authors.affiliation: Department of Oral Molecular Regulation, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kinbara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Funayama
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Takada
authors.forename: Shunji
authors.initials: S
authors.lastname: Sugawara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000818:Animals; D006640:Histidine Decarboxylase / Q000235:genetics; D006967:Hypersensitivity / Q000209:etiology* / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008351:Mannans / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009154:Mutation; D009532:Nickel / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000276:immunology; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000276:immunology; D018713:Prevotella intermedia / Q000737:chemistry / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D008351:Mannans; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D009532:Nickel; D006640:Histidine Decarboxylase