Article ; Online: Toll-like receptor 4 agonistic antibody promotes innate immunity against severe pneumonia induced by coinfection with influenza virus and Streptococcus pneumoniae.
Clinical and vaccine immunology : CVI
2013 Volume 20, Issue 7, Page(s) 977–985
Abstract: ... innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus and S ... 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 ...
| 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. |
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| MeSH term(s) | Animals ; Antibodies, Bacterial/immunology ; Body Weight ; Coinfection/immunology ; Coinfection/microbiology ; Coinfection/pathology ; Coinfection/virology ; Disease Models, Animal ; Histocytochemistry ; Humans ; Immunity, Innate ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred CBA ; Orthomyxoviridae/immunology ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/pathology ; Pneumococcal Infections/immunology ; Pneumococcal Infections/pathology ; Pneumonia/immunology ; Pneumonia/microbiology ; Pneumonia/pathology ; Pneumonia/virology ; Streptococcus pneumoniae/immunology ; Survival Analysis ; Toll-Like Receptor 4/agonists | |||||
| Chemical Substances | Antibodies, Bacterial ; Tlr4 protein, mouse ; Toll-Like Receptor 4 | |||||
| Language | English | |||||
| Publishing date | 2013-05-01 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2221082-9 | |||||
| ISSN | 1556-679X ; 1556-6811 | |||||
| ISSN (online) | 1556-679X | |||||
| ISSN | 1556-6811 | |||||
| DOI | 10.1128/CVI.00010-13 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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