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タイトル別表記
Clarithromycin expands CD11b+Gr-1+ MDSC-like cells
著者
Namkoong, Ho Keio University|Japan Society for the Promotion of Science
Ishii, Makoto Keio University
Yagi, Kazuma Keio University
Asami, Takahiro Keio University
Asakura, Takanori Keio University
Suzuki, Shoji Keio University
Hegab, Ahmed E. Keio University
Kamata, Hirofumi Keio University
Tasaka, Sadatomo Keio University
Atarashi, Koji Keio University
Nakamoto, Nobuhiro Keio University
Iwata, Satoshi Keio University
Honda, Kenya Keio University
Kanai, Takanori Keio University
Hasegawa, Naoki Keio University
Koyasu, Shigeo Keio University|RIKEN Center for Integrative Medical Sciences
Betsuyaku, Tomoko Keio University
資料タイプ
学術雑誌論文
抄録
Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+ cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+ cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+ cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage−HLA-DR−CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+ cells essential for the immunomodulatory properties of macrolides.
掲載誌名
PLOS Pathogens
ISSN
15537366
15537374
出版者
PLOS
14
4
開始ページ
e1006955
発行日
2018-04-05
権利情報
© 2018 Namkoong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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言語
eng
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出版社版
部局
歯学系