RRC ID 11212
Author Shida K, Kiyoshima-Shibata J, Kaji R, Nagaoka M, Nanno M.
Title Peptidoglycan from lactobacilli inhibits interleukin-12 production by macrophages induced by Lactobacillus casei through Toll-like receptor 2-dependent and independent mechanisms.
Journal Immunology
Abstract 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.
Volume 128(1 Suppl)
Pages e858-69
Published 2009-9-1
DOI 10.1111/j.1365-2567.2009.03095.x
PMID 19740347
PMC PMC2753894
MeSH Animals Cell Wall / immunology* Cells, Cultured Female Glycoside Hydrolases / pharmacology Immune Tolerance* Interleukin-12 / antagonists & inhibitors* Interleukin-12 / biosynthesis Interleukin-12 Subunit p35 / agonists Interleukin-12 Subunit p35 / immunology Interleukin-12 Subunit p40 / antagonists & inhibitors Interleukin-12 Subunit p40 / biosynthesis Lactobacillus casei / drug effects Lactobacillus casei / immunology* Macrophages, Peritoneal / immunology* Macrophages, Peritoneal / microbiology Mice Mice, Inbred BALB C Nod2 Signaling Adaptor Protein / metabolism Peptidoglycan / immunology* Phagocytosis / immunology Toll-Like Receptor 2 / immunology Tumor Necrosis Factor-alpha / agonists Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism
IF 5.016
Times Cited 50
General Microbes JCM 2012