Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae
Autor: | Katsunori Yanagihara, Yoshifumi Imamura, Shigeki Nakamura, Akitaka Tanaka, Shigeru Kohno, Masafumi Seki, Naoki Iwanaga, Kenji Fukudome, Koichi Izumikawa, Taiga Miyazaki, Hiroshi Kakeya |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Microbiology (medical)
Male Clinical Biochemistry Immunology Orthomyxoviridae macrophage Biology medicine.disease_cause Virus Pneumococcal Infections influenza virus Microbiology Mice Orthomyxoviridae Infections Immunity Streptococcus pneumoniae medicine Immunology and Allergy Animals Humans innate immunity Mice Inbred C3H Coinfection Histocytochemistry Body Weight Pneumonia medicine.disease biology.organism_classification Antibodies Bacterial Survival Analysis Immunity Innate Toll-Like Receptor 4 Pneumococcal infections Disease Models Animal Secondary bacterial pneumonia Pneumococcal pneumonia Mice Inbred CBA Clinical Immunology |
Zdroj: | Clinical and Vaccine Immunology. 20(7):977-985 |
ISSN: | 1556-6811 |
Popis: | 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. Clinical and Vaccine Immunology, 20(7), pp.977-985; 2013 |
Databáze: | OpenAIRE |
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