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Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae

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Title: Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae
Other Titles: Toll-Like Receptor 4アゴニスト抗体はインフルエンザウイルスと肺炎球菌の重複感染によって引き起こされる重症肺炎に対する自然免疫を賦活する
Authors: 田中, 章貴
Authors (alternative): Tanaka, Akitaka
Issue Date: 4-Sep-2013
Citation: Nagasaki University (長崎大学), 博士(医学) (2013-09-04)
Abstract: Coinfection with bacteria is a major cause of mortality during influenza epidemics. Recently, Toll-like receptor (TLR) agonists were shown to have immunomodulatory functions. In the present study, we investigated the effectiveness and mechanisms of the new TLR4 agonistic monoclonal antibody UT12 against secondary pneumococcal pneumonia induced by coinfection with influenza virus in a mouse model. Mice were intranasally inoculated with Streptococcus pneumoniae 2 days after influenza virus inoculation. UT12 was intraperitoneally administered 2 h before each inoculation. Survival rates were significantly increased and body weight loss was significantly decreased by UT12 administration. Additionally, the production of inflammatory mediators was significantly suppressed by the administration of UT12. In a histopathological study, pneumonia in UT12-treated mice was very mild compared to that in control mice. UT12 increased antimicrobial defense through the acceleration of macrophage recruitment into the lower respiratory tract induced by c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-κB) pathway- dependent monocyte chemoattractant protein 1 (MCP-1) production. Collectively, these findings indicate that UT12 promoted pulmonary innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus and S. pneumoniae. This immunomodulatory effect of UT12 improves the prognosis of secondary pneumococcal pneumonia and makes UT12 an attractive candidate for treating severe infectious diseases.
Description: 長崎大学学位論文 学位記番号:博(医歯薬)甲第619号 学位授与年月日:平成25年9月4日 / Author: Akitaka Tanaka, Shigeki Nakamura, Masafumi Seki, Kenji Fukudome, Naoki Iwanaga, Yoshifumi Imamura, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Kakeya, Katsunori Yanagihara , Shigeru Kohno / Citation: Clinical and Vaccine Immunology, 20(7), pp.977-985; 2013
Keywords: Secondary bacterial pneumonia / innate immunity / influenza virus / Streptococcus pneumoniae / macrophage
URI: http://hdl.handle.net/10069/35236
ISSN: 15566811
DOI: 10.1128/CVI.00010-13
Relational Links: http://hdl.handle.net/10069/34129
Rights: © 2013, American Society for Microbiology.
Type: Thesis or Dissertation
Text Version: ETD
Appears in Collections:dissertation

Citable URI : http://hdl.handle.net/10069/35236

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