Early production of tumor necrosis factor-α by Gr-1+ cells and its role in the host defense to pneumococcal infection in lungs

Masumitsu Hatta, Natsuo Yamamoto, Akiko Miyazato, Naoto Ishii, Kiwamu Nakamura, Ken Inden, Tetsuji Aoyagi, Hiroyuki Kunishima, Yoichi Hirakata, Kazuo Suzuki, Mitsuo Kaku, Kazuyoshi Kawakami

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


In this study, we elucidated the role of tumor necrosis factor (TNF)-α in the host defense to pulmonary infection with Streptococcus pneumoniae and defined the cellular source of this cytokine at an early stage of infection. Administration of anti-TNF-α monoclonal antibody (mAb) resulted in the reduced accumulation of neutrophils in bronchoalveolar lavage fluids (BALFs) and severe exacerbation of this infection. In a flow cytometric analysis, the intracellular expression of TNF-α was detected in Gr-1 bright+ and Gr-1dull+ cells during the time intervals postinfection, and F4/80+ cells expressed intracellular TNF-α before Gr-1dull+ cells appeared. The Gr-1bright+ and Gr-1dull+ cells sorted from BALF cells at 24 h were identified as neutrophils and macrophage-like cells, respectively, and the Gr-1 dull+ cells expressing CD11c, partially CD11b and a marginal level of F4/80 secreted TNF-α in in vitro cultures. Finally, deletion of Gr-1 + cells by administration of the specific mAb significantly reduced the concentrations of this cytokine in BALF at 6 and 12 h postinfection, but not the expression of TNF-α in F4/80+ cells. Thus, these results demonstrated that neutrophils, F4/80+ macrophages and Gr-1 dull+ CD11c+ macrophage-like cells played an important role in the production of TNF-α in lungs at an early stage of infection with S. pneumoniae.

Original languageEnglish
Pages (from-to)182-192
Number of pages11
JournalFEMS Immunology and Medical Microbiology
Issue number2
Publication statusPublished - 2010 Mar


  • Neutrophils
  • Pneumococcal infection
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases


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