title: Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids.
abstract: Lipoteichoic acid (LTA) is a major immunostimulating component in the cell wall of Gram-positive bacteria as lipopolysaccharide of Gram-negative bacteria. However, LTA is expressed on not only pathogenic but also nonpathogenic Gram-positive bacteria. In order to examine whether the immunostimulating potentials of Gram-positive bacteria are correlated with their LTAs, we prepared highly pure LTAs from Staphylococcus aureus (pathogenic), Bacillus subtilis (non-pathogenic), or Lactobacillus plantarum (beneficial). When a murine macrophage cell-line, RAW 264.7, was stimulated with heat-killed bacteria, both S. aureus and B. subtilis induced nitric oxide (NO) production in a dose-dependent manner while L. plantarum showed a minimal induction. Interestingly, purified LTAs from S. aureus and B. subtilis, but not from L. plantarum, were able to induce the production of NO. The differential inflammatory potentials of LTAs coincided with their abilities to activate Toll-like receptor 2 (TLR2), which is known to recognize Gram-positive bacteria and LTA, and transcription factors NF-kappaB and AP-1. Similar results were obtained with the expression of cytokines related to inflammation by RAW 264.7 and human peripheral blood mononuclear cells as well. The ability of LTA to induce TNF-alpha and NO production was abolished when the LTAs were treated with 0.2 N NaOH. Collectively, we suggest that the immunostimulating potentials of Gram-positive bacteria differ due to their LTAs with differential potencies in the stimulation of TLR2.
authors.affiliation: Department of Oral Microbiology & Immunology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Ryu
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Baik
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Yang
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
authors.forename: Jintaek
authors.initials: J
authors.lastname: Im
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Kangseok
authors.initials: K
authors.lastname: Lee
authors.forename: Dae Kyun
authors.initials: DK
authors.lastname: Chung
authors.forename: Hyang Ran
authors.initials: HR
authors.lastname: Ju
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001412:Bacillus subtilis / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D006094:Gram-Positive Bacteria / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D007202:Indicators and Reagents; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D048191:Lactiplantibacillus plantarum / Q000737:chemistry; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000737:chemistry; D013682:Teichoic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007202:Indicators and Reagents; D053645:Interleukin-2 Receptor alpha Subunit; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C009900:lipoteichoic acid