Nickel allergy-promoting effects of microbial or inflammatory substances at the sensitization step in mice

作者：Takahashi Harue; Kinbara Masayuki; Sato Naoki; Sasaki Keiichi; Sugawara Shunji; Endo Yasuo^*

来源：International Immunopharmacology, 2011, 11(10): 1534-1540.

DOI：10.1016/j.intimp.2011.05.010

• Allergy
• Nickel
• Adjuvant
• Infection
• Innate immunity

Microbial components stimulate innate immunity via Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and/or IL-1. We recently reported that in mice, Escherichia coli lipopolysaccharide (LPS, TLR4-ligand) promotes allergic responses to nickel (Ni) at both the sensitization and elicitation steps. Here, we examined in mice the effects of administering other microbial or inflammatory materials at the Ni-sensitization step. A mixture of 1 mM NiCl(2) and a test solution was injected into BALB/c mice intraperitoneally (0.1 ml/10 g body weight), and 10 days later 5 mM NiCl(2) was challenged intradermally into the ear pinnas of the mice (20 mu l/ear). The following preparations or substances exhibited adjuvant activities: Prevotella intermedia LPS. Saccharomyces cerevisiae mannan, a synthetic muramyl dipeptide (NOD2-stimulating cell-wall component of bacteria), Pam(3)Cys-SKKKK (TLR2-stimulating synthetic peptide), poly I:C (TLR3-stimulating double-stranded RNA), concanavalin A (a typical T-cell mitogen and T-cell-mediated hepatitis-inducer), heat-killed Propionibacterium acnes (Gram-positive bacterium that causes pimples and induces macrophage-mediated experimental hepatitis), and nitrogen-containing bisphosphonates (chemicals stimulating IL-1 production). Unexpectedly, P. intermedia LPS, which displayed the most potent adjuvant activity among the tested preparations, was effective in TLR4-dysfunctional mutant mice, but not in TLR2-deficient mice, whereas the reverse was true for S. cerevisiae mannan. These results suggest that (i) for the establishment of Ni-allergy in mice, stimulation of innate immunity (including TLRs, NLRs, IL-1 production, and/or other factors) may be important at the sensitization step, and (ii) P. intermedia may produce a substance(s) that potently promotes Ni-allergy via stimulation of TLR2.

• 出版日期2011-10