Role of interferon-γ in Vα14+ natural killer T cell-mediated host defense against Streptococcus pneumoniae infection in murine lungs

Masashi Nakamatsu, Natsuo Yamamoto, Masumitsu Hatta, Chikara Nakasone, Takeshi Kinjo, Kazuya Miyagi, Kaori Uezu, Kiwamu Nakamura, Toshinori Nakayama, Masaru Taniguchi, Yoichiro Iwakura, Mitsuo Kaku, Jiro Fujita, Kazuyoshi Kawakami

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Previously, we demonstrated that Vα14+ NKT cells and IFN-γ are important upstream components in neutrophil-mediated host defense against infection with Streptococcus pneumoniae. In the present study, we extended these findings by elucidating the role of IFN-γ in this Vα14+ NKT cell-promoted process. Administration of recombinant IFN-γ to Jα18KO mice prolonged the shortened survival, promoted the attenuated clearance of bacteria and improved the reduced accumulation of neutrophils and synthesis of MIP-2 and TNF-α in the lungs, in comparison to wild-type (WT) mice. In addition, intravenous transfer of liver mononuclear cells (LMNC) from WT mice into Jα18KO mice resulted in complete recovery of the depleted responses listed above, whereas such effects were not detected when LMNC were obtained from IFN-γKO or Jα18KO mice. Activation of Vα14+ NKT cells by α-galactosylceramide (α-GalCer) significantly enhanced the clearance of bacteria, accumulation of neutrophils and synthesis of MIP-2 and TNF-α in the infected lungs; this effect was significantly inhibited by a neutralizing anti-IFN-γ antibody. Finally, in a flow cytometric analysis, TNF-α synthesis was detected largely by CD11bbright+ cells in the infected lungs. Our results demonstrated that IFN-γ plays an important role in the neutrophil-mediated host protective responses against pneumococcal infection promoted by Vα14+ NKT cells.

Original languageEnglish
Pages (from-to)364-374
Number of pages11
JournalMicrobes and Infection
Volume9
Issue number3
DOIs
Publication statusPublished - 2007 Mar

Keywords

  • Chemokine
  • IFN-γ
  • Lung
  • Mouse
  • NKT cells
  • Neutrophils
  • Pneumococcal infection

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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