Bacillus anthracis genomic DNA enhances lethal toxin-induced cytotoxicity through TNF-alpha production
DC Field | Value | Language |
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dc.contributor.author | Jeon, Jun Ho | - |
dc.contributor.author | Kim, Yeon Hee | - |
dc.contributor.author | Choi, Min Kyung | - |
dc.contributor.author | Kim, Kyung Ae | - |
dc.contributor.author | Lee, Hae-Ri | - |
dc.contributor.author | Jang, Jeyoun | - |
dc.contributor.author | Kim, Yu-Ri | - |
dc.contributor.author | Chun, Jeong-Hoon | - |
dc.contributor.author | Eo, Seong Kug | - |
dc.contributor.author | Kim, Tae Sung | - |
dc.contributor.author | Rhie, Gi-eun | - |
dc.date.accessioned | 2021-09-05T02:14:48Z | - |
dc.date.available | 2021-09-05T02:14:48Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2014-12-04 | - |
dc.identifier.issn | 1471-2180 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/96531 | - |
dc.description.abstract | Background: Bacillus anthracis is the etiological agent of anthrax. Lethal toxin (LT) produced by B. anthracis is a well-known key virulence factor for anthrax because of its strong cytotoxic activity. However, little is known about the role of B. anthracis genomic DNA (BAG) in anthrax pathogenesis. Results: We examined the effect of BAG on TNF-alpha production and LT-mediated cytotoxicity during B. anthracis spore infection in mouse macrophage cell lines (RAW264.7 cells and J774A.1) and BALB/c mice. Infection of RAW264.7 cells with B. anthracis spores induced TNF-alpha expression in a multiplicity of infection (MOI)-dependent manner, and this enhancement was attenuated by the toll-like receptor (TLR) 9 inhibitor oligodeoxynucleotide (ODN)2088. BAG led to TNF-alpha expression in a dose-and time-dependent manner when applied to RAW264.7 cells. TNF-alpha expression induced by BAG was reduced by either pretreatment with TLR9 inhibitors (ODN2088 and chloroquine (CQ)) or transfection with TLR9 siRNA. Furthermore, BAG-induced TNF-alpha production in TLR9(+/+) macrophages was completely abrogated in TLR9-/-macrophages. BAG enhanced the phosphorylation of mitogen-activated protein kinases (MAPK), and BAG-induced TNF-alpha expression was attenuated by pretreatment with MAPK inhibitors. A reporter gene assay and confocal microscopy demonstrated that BAG increased NF-kappa B activation, which is responsible for TNF-alpha expression. Treatment with BAG alone showed no cytotoxic activity on the macrophage cell line J774A. 1, whereas LT-mediated cytotoxicity was enhanced by treatment with BAG or TNF-alpha. Enhanced LT-induced lethality was also confirmed by BAG administration in mice. Furthermore, LT plus BAG-mediated lethality was significantly recovered by administration of Infliximab, an anti-TNF-alpha monoclonal antibody. Conclusions: Our results suggest that B. anthracis DNA may contribute to anthrax pathogenesis by enhancing LT activity via TLR9-mediated TNF-alpha production. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | BIOMED CENTRAL LTD | - |
dc.subject | NECROSIS-FACTOR-ALPHA | - |
dc.subject | TOLL-LIKE RECEPTORS | - |
dc.subject | NF-KAPPA-B | - |
dc.subject | BACTERIAL-DNA | - |
dc.subject | INNATE IMMUNITY | - |
dc.subject | MACROPHAGE ACTIVATION | - |
dc.subject | VASCULAR LEAKAGE | - |
dc.subject | CELL-DEATH | - |
dc.subject | IN-VIVO | - |
dc.subject | MICE | - |
dc.title | Bacillus anthracis genomic DNA enhances lethal toxin-induced cytotoxicity through TNF-alpha production | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Tae Sung | - |
dc.identifier.doi | 10.1186/s12866-014-0300-9 | - |
dc.identifier.scopusid | 2-s2.0-84924192376 | - |
dc.identifier.wosid | 000347012500001 | - |
dc.identifier.bibliographicCitation | BMC MICROBIOLOGY, v.14 | - |
dc.relation.isPartOf | BMC MICROBIOLOGY | - |
dc.citation.title | BMC MICROBIOLOGY | - |
dc.citation.volume | 14 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Microbiology | - |
dc.relation.journalWebOfScienceCategory | Microbiology | - |
dc.subject.keywordPlus | NECROSIS-FACTOR-ALPHA | - |
dc.subject.keywordPlus | TOLL-LIKE RECEPTORS | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | BACTERIAL-DNA | - |
dc.subject.keywordPlus | INNATE IMMUNITY | - |
dc.subject.keywordPlus | MACROPHAGE ACTIVATION | - |
dc.subject.keywordPlus | VASCULAR LEAKAGE | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordAuthor | Bacillus anthracis | - |
dc.subject.keywordAuthor | Genomic DNA | - |
dc.subject.keywordAuthor | Lethal toxin | - |
dc.subject.keywordAuthor | TLR9 | - |
dc.subject.keywordAuthor | TNF-alpha | - |
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