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Peptidoglycan from lactobacilli inhibits interleukin‐12 production by macrophages induced by Lactobacillus casei through Toll‐like receptor 2‐dependent and independent mechanisms
Author(s) -
Shida Kan,
KiyoshimaShibata Junko,
Kaji Rumi,
Nagaoka Masato,
Nanno Masanobu
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03095.x
Subject(s) - peptidoglycan , lactobacillus casei , muramyl dipeptide , microbiology and biotechnology , tlr2 , biology , intracellular , lipoteichoic acid , lactobacillus , biochemistry , cell wall , receptor , bacteria , staphylococcus aureus , tlr4 , in vitro , fermentation , genetics
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 inhibited L. 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.