Peptidoglycan from lactobacilli inhibits interleukin-12 production by macrophages induced by Lactobacillus casei through Toll-like receptor 2-dependent and independent mechanisms

We previously showed that Lactobacillus strains having a rigid cell wall resistant to intracellular digestion can stimulate macrophages to induce large a quantity of interleukin-12 (IL-12). In this study, we examined the influence of lactobacilli and bacterial cell wall components on IL-12 productio...

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Published inImmunology Vol. 128; no. 1pt2; pp. e858 - e869
Main Authors Shida, Kan, Kiyoshima-Shibata, Junko, Kaji, Rumi, Nagaoka, Masato, Nanno, Masanobu
Format Journal Article
LanguageEnglish
Published Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.09.2009
Blackwell Publishing Ltd
Blackwell Science Inc
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Summary:We previously showed that Lactobacillus strains having a rigid cell wall resistant to intracellular digestion can stimulate macrophages to induce large a quantity of interleukin-12 (IL-12). In this study, we examined the influence of lactobacilli and bacterial cell wall components on IL-12 production by macrophages that was induced by Lactobacillus casei, which has a rigid cell wall. Easily digestible lactobacilli such as Lactobacillus johnsonii and Lactobacillus plantarum or their intact cell walls (ICWs) weakly or very weakly induced IL-12 production by macrophages, and inhibitedL. casei-induced IL-12 production. While the ICW of L. casei was resistant to intracellular digestion and did not inhibit L. casei-induced IL-12 production, its polysaccharide-depleted ICW, i.e. intact peptidoglycan, was sensitive to intracellular digestion and inhibited L. casei-induced IL-12 production. Furthermore, the peptidoglycans of L. johnsonii, L. plantarum and Staphylococcus aureus also inhibited L. casei-induced IL-12 production. Peptidoglycans from lactobacilli suppressed L. casei-induced expression of IL-12p40 but not IL-12p35 mRNA. Inhibition of IL-12 production by peptidoglycan was mitigated in Toll-like receptor 2 (TLR2)-deficient macrophages compared with the inhibition in wild-type macrophages. A derivative of the minimal structural unit of peptidoglycan (6-O-stearoyl-muramyl dipeptide) recognized by nucleotide-binding oligomerization domain 2 (NOD2) could also suppress L. casei-induced IL-12 production. These findings demonstrate that easily digestible bacteria and peptidoglycan suppress IL-12 production through pattern recognition receptors such as TLR2 and NOD2. IL-12 production in the gut may be negatively regulated by the simultaneous inhibitory actions of various resident bacteria that are susceptible to intracellular digestion.
Bibliography:http://dx.doi.org/10.1111/j.1365-2567.2009.03095.x
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Please cite this article in press as: Shida K. et al. Peptidoglycan from lactobacilli inhibits interleukin-12 production by macrophages induced by Lactobacillus casei through Toll-like receptor 2-dependent and independent mechanisms, Immunology (2009)
ISSN:0019-2805
1365-2567
DOI:10.1111/j.1365-2567.2009.03095.x