title: Bacillus anthracis lethal toxin attenuates lipoteichoic acid-induced maturation and activation of dendritic cells through a unique mechanism.
abstract: Lethal toxin (LT), produced by the gram-positive bacterium Bacillus anthracis, was identified as a major etiologic agent causing anthrax due to its strong immunotoxicity. Gram-positive bacteria express lipoteichoic acid (LTA), which is considered as a counterpart to lipopolysaccharide (LPS) of gram-negative bacteria, but differs from LPS in the structure and function. Since dendritic cells (DCs) are essential for the appropriate initiation of immune response, we investigated the effect of LT on LTA-induced DC maturation using immature DCs prepared by differentiation of C57BL/6 mouse bone marrow cells. When immature DCs were matured with LTA in the presence of LT, the expression of representative markers for DC maturation such as CD80, CD83, and CD86 together with MHC class I and II molecules was inhibited. LT ameliorated the attenuation of endocytic capacity during DC maturation by LTA while such effect was not observed in LPS-matured DCs. Furthermore, exposure to LT resulted in a decrease in the expression of pro-inflammatory cytokines including IL-6, TNF-alpha, and IL-12p40 in LTA-stimulated DCs as in LPS-stimulated DCs. Interestingly, LT showed a minimal change in LTA-induced IL-1beta expression while LT highly enhanced the LPS-induced IL-1beta expression. Those inhibitory effects might be associated with LT interference of LTA-signaling pathways mediated through mitogen-activated protein kinases (MAPKs) since LT suppressed phosphorylation of MAPK, which was induced by LTA. Meanwhile, no change was observed in the expression of putative anthrax toxin receptors, TEM8 and CMG2, or Toll-like receptor 2. These results suggest that LT suppresses the maturation and activation of DCs stimulated with LTA, similar to the suppression in the LPS-stimulated DCs, but via a distinct mechanism.
authors.affiliation: Department of Oral Microbiology & Immunology, BK21 Program, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Yang
authors.forename: Sang Su
authors.initials: SS
authors.lastname: Woo
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Ryu
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Cho
authors.forename: Gi-Eun
authors.initials: GE
authors.lastname: Rhie
authors.forename: Bong-Su
authors.initials: BS
authors.lastname: Kim
authors.forename: Hee-Bok
authors.initials: HB
authors.lastname: Oh
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D001854:Bone Marrow Cells / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008840:Microfilament Proteins; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000276:immunology; D013682:Teichoic Acids / Q000276:immunology / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D015703:Antigens, CD; C523012:Antxr1 protein, mouse; C523013:Antxr2 protein, mouse; D001427:Bacterial Toxins; D014408:Biomarkers, Tumor; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C030325:anthrax toxin; C440499:lipopolysaccharide, Escherichia coli O111 B4; C009900:lipoteichoic acid