PMID- 23637040
OWN - NLM
STAT- MEDLINE
DCOM- 20140121
LR  - 20211021
IS  - 1556-679X (Electronic)
IS  - 1556-6811 (Print)
IS  - 1556-679X (Linking)
VI  - 20
IP  - 7
DP  - 2013 Jul
TI  - Toll-like receptor 4 agonistic antibody promotes innate immunity against severe 
      pneumonia induced by coinfection with influenza virus and Streptococcus 
      pneumoniae.
PG  - 977-85
LID - 10.1128/CVI.00010-13 [doi]
AB  - 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-kappaB) 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.
FAU - Tanaka, Akitaka
AU  - Tanaka A
AD  - Department of Molecular Microbiology and Immunology, Nagasaki University Graduate 
      School of Biomedical Sciences, Nagasaki University School of Medicine, Nagasaki, 
      Japan.
FAU - Nakamura, Shigeki
AU  - Nakamura S
FAU - Seki, Masafumi
AU  - Seki M
FAU - Fukudome, Kenji
AU  - Fukudome K
FAU - Iwanaga, Naoki
AU  - Iwanaga N
FAU - Imamura, Yoshifumi
AU  - Imamura Y
FAU - Miyazaki, Taiga
AU  - Miyazaki T
FAU - Izumikawa, Koichi
AU  - Izumikawa K
FAU - Kakeya, Hiroshi
AU  - Kakeya H
FAU - Yanagihara, Katsunori
AU  - Yanagihara K
FAU - Kohno, Shigeru
AU  - Kohno S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130501
PL  - United States
TA  - Clin Vaccine Immunol
JT  - Clinical and vaccine immunology : CVI
JID - 101252125
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Antibodies, Bacterial/*immunology
MH  - Body Weight
MH  - Coinfection/*immunology/microbiology/pathology/virology
MH  - Disease Models, Animal
MH  - Histocytochemistry
MH  - Humans
MH  - *Immunity, Innate
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred CBA
MH  - Orthomyxoviridae/immunology
MH  - Orthomyxoviridae Infections/*immunology/pathology
MH  - Pneumococcal Infections/*immunology/pathology
MH  - Pneumonia/*immunology/microbiology/pathology/virology
MH  - Streptococcus pneumoniae/immunology
MH  - Survival Analysis
MH  - Toll-Like Receptor 4/*agonists
PMC - PMC3697446
EDAT- 2013/05/03 06:00
MHDA- 2014/01/22 06:00
PMCR- 2014/01/01
CRDT- 2013/05/03 06:00
PHST- 2013/05/03 06:00 [entrez]
PHST- 2013/05/03 06:00 [pubmed]
PHST- 2014/01/22 06:00 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - CVI.00010-13 [pii]
AID - 00010-13 [pii]
AID - 10.1128/CVI.00010-13 [doi]
PST - ppublish
SO  - Clin Vaccine Immunol. 2013 Jul;20(7):977-85. doi: 10.1128/CVI.00010-13. Epub 2013 
      May 1.