Bacterial Teichoic Acids Reverse Predominant IL-12 Production Induced by Certain Lactobacillus Strains into Predominant IL-10 Production via TLR2-Dependent ERK Activation in Macrophages

• Published in: The Journal of immunology (1950) 2010-04, Vol.184 (7), p.3505-3513
• Main Authors: Kaji, Rumi, Kiyoshima-Shibata, Junko, Nagaoka, Masato, Nanno, Masanobu, Shida, Kan
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Cell Separation; Enzyme Activation - immunology; Extracellular Signal-Regulated MAP Kinases - immunology; Female; Flow Cytometry; Interleukin-10 - biosynthesis; Interleukin-10 - immunology; Interleukin-12 - biosynthesis; Interleukin-12 - immunology; Lactobacillus - immunology; Macrophages, Peritoneal - enzymology; Macrophages, Peritoneal - immunology; Mice; Mice, Inbred BALB C; RNA, Messenger - analysis; Signal Transduction - immunology; Teichoic Acids - immunology; Toll-Like Receptor 2 - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0901569

The cytokine response of macrophages to probiotic lactobacilli varies between strains, and the balance of IL-10/IL-12 production is crucial for determination of the direction of the immune response. To clarify the mechanism whereby Lactobacillus strains differentially induce production of IL-10 and IL-12, we examined the potential relationship between cytokine production and MAPK activation. In mouse peritoneal macrophages, Lactobacillus plantarum potently induced IL-10 but weakly induced IL-12 production, whereas L. casei potently induced IL-12 but weakly induced IL-10 production. Kinetic analysis of the activation of ERK, p38, and JNK showed that L. plantarum induced a more rapid and intense activation of MAPKs, especially of ERK, than L. casei. A selective blockade of ERK activation induced by L. plantarum resulted in a decrease in IL-10 production and a simultaneous increase in IL-12 production. Interestingly, when macrophages were stimulated with a combination of L. plantarum and L. casei, IL-10 production was induced synergistically. We identified cell wall teichoic acid and lipoteichoic acid as key factors for triggering the synergistic induction of IL-10 production, although these teichoic acids alone only weakly induced IL-10 production. The effect of these teichoic acids on IL-10 production was mediated by TLR2-dependent ERK activation. Our data demonstrate that activation of the ERK pathway is critical for determination of the balance of the IL-10/IL-12 response of macrophages to lactobacilli and that predominant IL-12 production induced by certain lactobacilli such as L. casei can be converted into predominant IL-10 production when stimulated in the presence of teichoic acids.