title: Toll-like receptor 4 agonistic antibody promotes innate immunity against severe pneumonia induced by coinfection with influenza virus and Streptococcus pneumoniae.
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.
authors: Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki, Japan.
authors: Akitaka
authors: A
authors: Tanaka
authors: Shigeki
authors: S
authors: Nakamura
authors: Masafumi
authors: M
authors: Seki
authors: Kenji
authors: K
authors: Fukudome
authors: Naoki
authors: N
authors: Iwanaga
authors: Yoshifumi
authors: Y
authors: Imamura
authors: Taiga
authors: T
authors: Miyazaki
authors: Koichi
authors: K
authors: Izumikawa
authors: Hiroshi
authors: H
authors: Kakeya
authors: Katsunori
authors: K
authors: Yanagihara
authors: Shigeru
authors: S
authors: Kohno
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001835:Body Weight; D060085:Coinfection / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000473:pathology; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D013296:Streptococcus pneumoniae / Q000276:immunology; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000819:agonists*
chemical_list: D000907:Antibodies, Bacterial; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
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