The elicitation step of nickel allergy is promoted in mice by microbe-related substances, including some from oral bacteria

Ling Huang, Masayuki Kinbara, Hiromi Funayama, Haruhiko Takada, Shunji Sugawara, Yasuo Endo

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1916-1924
Number of pages9
JournalInternational Immunopharmacology
Issue number11
Publication statusPublished - 2011 Nov


  • Innate immunity
  • Lipopolysaccharide
  • Mannan
  • Nickel allergy
  • Oral bacteria


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