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Bacillus anthracis genomic DNA enhances lethal toxin-induced cytotoxicity through TNF-α production.
Jeon, Jun Ho; Kim, Yeon Hee; Choi, Min Kyung; Kim, Kyung Ae; Lee, Hae-Ri; Jang, Jeyoun; Kim, Yu-Ri; Chun, Jeong-Hoon; Eo, Seong Kug; Kim, Tae Sung; Rhie, Gi-Eun.
Afiliação
  • Jeon JH; Division of High-risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 361-951, Republic of Korea. sasujun@hanmail.net.
  • Kim YH; Division of High-risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 361-951, Republic of Korea. hanikim@hanmail.net.
  • Choi MK; School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea. hanikim@hanmail.net.
  • Kim KA; Division of High-risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 361-951, Republic of Korea. mk6214@hanmail.net.
  • Lee HR; Division of High-risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 361-951, Republic of Korea. kkaml3@hanmail.net.
  • Jang J; Division of High-risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 361-951, Republic of Korea. haeruili@hotmail.com.
  • Kim YR; Division of High-risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 361-951, Republic of Korea. zzang9575@empas.com.
  • Chun JH; Division of High-risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 361-951, Republic of Korea. eul62@naver.com.
  • Eo SK; Division of High-risk Pathogen Research, Center for Infectious Diseases, National Institute of Health, 187 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungbuk, 361-951, Republic of Korea. hg1117@korea.kr.
  • Kim TS; College of Veterinary medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju, 561-765, Republic of Korea. vetvirus@chonbuk.ac.kr.
  • Rhie GE; School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea. tskim@korea.ac.kr.
BMC Microbiol ; 14: 300, 2014 Dec 04.
Article em En | MEDLINE | ID: mdl-25472474
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-α 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-α 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-α expression in a dose- and time-dependent manner when applied to RAW264.7 cells. TNF-α 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-α production in TLR9(+/+) macrophages was completely abrogated in TLR9(-/-) macrophages. BAG enhanced the phosphorylation of mitogen-activated protein kinases (MAPK), and BAG-induced TNF-α expression was attenuated by pretreatment with MAPK inhibitors. A reporter gene assay and confocal microscopy demonstrated that BAG increased NF-κB activation, which is responsible for TNF-α 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-α. 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-α monoclonal antibody. CONCLUSIONS: Our results suggest that B. anthracis DNA may contribute to anthrax pathogenesis by enhancing LT activity via TLR9-mediated TNF-α production.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bacillus anthracis / Toxinas Bacterianas / DNA Bacteriano / Fator de Necrose Tumoral alfa / Antraz / Antígenos de Bactérias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: BMC Microbiol Assunto da revista: MICROBIOLOGIA Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bacillus anthracis / Toxinas Bacterianas / DNA Bacteriano / Fator de Necrose Tumoral alfa / Antraz / Antígenos de Bactérias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: BMC Microbiol Assunto da revista: MICROBIOLOGIA Ano de publicação: 2014 Tipo de documento: Article