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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)302-313
Number of pages12
JournalCytotherapy
Volume20
Issue number3
DOIs
Publication statusPublished - 2018 Mar 1

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Pneumococcal Infections
Mesenchymal Stromal Cells
Anti-Inflammatory Agents
Lung
Streptococcus pneumoniae
Bronchoalveolar Lavage Fluid
Conditioned Culture Medium
Interleukin-6
Pneumonia
Macrophages
Pneumococcal Pneumonia
Ligands
Toll-Like Receptor 2
Bone and Bones
Bacterial Load
Granulocyte-Macrophage Colony-Stimulating Factor
Innate Immunity
Interleukin-10
Peroxidase
Cause of Death

Keywords

  • cell therapy
  • mesenchymal stromal cells
  • pneumonia
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

Cite this

Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus pneumoniae pulmonary infection in mice. / Asami, Takahiro; Ishii, Makoto; Namkoong, Ho; Yagi, Kazuma; Tasaka, Sadatomo; Asakura, Takanori; Suzuki, Shoji; Kamo, Tetsuro; Okamori, Satoshi; Kamata, Hirofumi; Zhang, Haiyue; Hegab, Ahmed E.; Hasegawa, Naoki; Betsuyaku, Tomoko.

In: Cytotherapy, Vol. 20, No. 3, 01.03.2018, p. 302-313.

Research output: Contribution to journalArticle

Asami, T, Ishii, M, Namkoong, H, Yagi, K, Tasaka, S, Asakura, T, Suzuki, S, Kamo, T, Okamori, S, Kamata, H, Zhang, H, Hegab, AE, Hasegawa, N & Betsuyaku, T 2018, 'Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus pneumoniae pulmonary infection in mice', Cytotherapy, vol. 20, no. 3, pp. 302-313. https://doi.org/10.1016/j.jcyt.2018.01.003
Asami, Takahiro ; Ishii, Makoto ; Namkoong, Ho ; Yagi, Kazuma ; Tasaka, Sadatomo ; Asakura, Takanori ; Suzuki, Shoji ; Kamo, Tetsuro ; Okamori, Satoshi ; Kamata, Hirofumi ; Zhang, Haiyue ; Hegab, Ahmed E. ; Hasegawa, Naoki ; Betsuyaku, Tomoko. / Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus pneumoniae pulmonary infection in mice. In: Cytotherapy. 2018 ; Vol. 20, No. 3. pp. 302-313.
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AU - Asakura, Takanori

AU - Suzuki, Shoji

AU - Kamo, Tetsuro

AU - Okamori, Satoshi

AU - Kamata, Hirofumi

AU - Zhang, Haiyue

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AU - Hasegawa, Naoki

AU - Betsuyaku, Tomoko

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N2 - 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.

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