Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus pneumoniae pulmonary infection in mice

Takahiro Asami, Makoto Ishii, Ho Namkoong, Kazuma Yagi, Sadatomo Tasaka, Takanori Asakura, Shoji Suzuki, Tetsuro Kamo, Satoshi Okamori, Hirofumi Kamata, Haiyue Zhang, Ahmed E. Hegab, Naoki Hasegawa, Tomoko Betsuyaku

研究成果: Article査読

22 被引用数 (Scopus)

抄録

Background: Pneumonia is the fourth leading cause of death worldwide, and Streptococcus pneumoniae is the most commonly associated pathogen. Increasing evidence suggests that mesenchymal stromal cells (MSCs) have anti-inflammatory roles during innate immune responses such as sepsis. However, little is known about the effect of MSCs on pneumococcal pneumonia. Methods: Bone marrow–derived macrophages (BMDMs) were stimulated with various ligands in the presence or absence of MSC-conditioned medium. For in vivo studies, mice intranasally-inoculated with S. pneumoniae were intravenously treated with MSCs or vehicle, and various parameters were assessed. Results: After stimulation with toll-like receptor (TLR) 2, TLR9 or TLR4 ligands, or live S. pneumoniae, TNF-α and interleukin (IL)–6 levels were significantly decreased, whereas IL-10 was significantly increased in BMDMs cultured in MSC-conditioned medium. In mice, MSC treatment decreased the number of neutrophils in bronchoalveolar lavage fluid (BALF) after pneumococcal infection, and this was associated with a decrease in myeloperoxidase activity in the lungs. Levels of proinflammatory cytokines, including TNF-α IL-6, GM-CSF and IFN-γ were significantly lower in MSC-treated mice, and the bacterial load in the lung after pneumococcal infection was significantly reduced. In addition, histopathologic analysis confirmed a decrease in the number of cells recruited to the lungs; however, lung edema, protein leakage into the BALF and levels of the antibacterial protein lipocalin 2 in the BALF were comparable between the groups. Conclusions: These results indicate that MSCs could represent a potential therapeutic application for the treatment of pneumonia caused by S. pneumoniae.

本文言語English
ページ(範囲)302-313
ページ数12
ジャーナルCytotherapy
20
3
DOI
出版ステータスPublished - 2018 3月

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学
  • 腫瘍学
  • 遺伝学(臨床)
  • 細胞生物学
  • 癌研究
  • 移植

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