Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids.
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.
Ryu
Young Hee
YH
Department of Oral Microbiology & Immunology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Baik
Jung Eun
JE
Yang
Jae Seung
JS
Kang
Seok-Seong
SS
Im
Jintaek
J
Yun
Cheol-Heui
CH
Kim
Dong Wook
DW
Lee
Kangseok
K
Chung
Dae Kyun
DK
Ju
Hyang Ran
HR
Han
Seung Hyun
SH
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
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