Role of interferon-gamma in Valpha14+ natural killer T cell-mediated host defense against Streptococcus pneumoniae infection in murine lungs

Previously, we demonstrated that Valpha14+ NKT cells and IFN-gamma 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-gamma in this Valpha14+ NKT cell-p...

Full description

Saved in:
Bibliographic Details
Published in:Microbes and infection 2007-03, Vol.9 (3), p.364-374
Main Authors: Nakamatsu, Masashi, Yamamoto, Natsuo, Hatta, Masumitsu, Nakasone, Chikara, Kinjo, Takeshi, Miyagi, Kazuya, Uezu, Kaori, Nakamura, Kiwamu, Nakayama, Toshinori, Taniguchi, Masaru, Iwakura, Yoichiro, Kaku, Mitsuo, Fujita, Jiro, Kawakami, Kazuyoshi
Format: Article
Language:English
Subjects:
Animals
Chemokines - metabolism
Humans
Interferon-gamma - genetics
Interferon-gamma - metabolism
Killer Cells, Natural - immunology
Lung - immunology
Lung - microbiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils - immunology
Pneumonia, Pneumococcal - immunology
Pneumonia, Pneumococcal - microbiology
Pneumonia, Pneumococcal - mortality
Receptors, Antigen, T-Cell, alpha-beta - genetics
Receptors, Antigen, T-Cell, alpha-beta - metabolism
Streptococcus pneumoniae - immunology
Streptococcus pneumoniae - pathogenicity
T-Lymphocyte Subsets - immunology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Previously, we demonstrated that Valpha14+ NKT cells and IFN-gamma 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-gamma in this Valpha14+ NKT cell-promoted process. Administration of recombinant IFN-gamma to Jalpha18KO 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-alpha in the lungs, in comparison to wild-type (WT) mice. In addition, intravenous transfer of liver mononuclear cells (LMNC) from WT mice into Jalpha18KO mice resulted in complete recovery of the depleted responses listed above, whereas such effects were not detected when LMNC were obtained from IFN-gammaKO or Jalpha18KO mice. Activation of Valpha14+ NKT cells by alpha-galactosylceramide (alpha-GalCer) significantly enhanced the clearance of bacteria, accumulation of neutrophils and synthesis of MIP-2 and TNF-alpha in the infected lungs; this effect was significantly inhibited by a neutralizing anti-IFN-gamma antibody. Finally, in a flow cytometric analysis, TNF-alpha synthesis was detected largely by CD11b(bright+) cells in the infected lungs. Our results demonstrated that IFN-gamma plays an important role in the neutrophil-mediated host protective responses against pneumococcal infection promoted by Valpha14+ NKT cells.
ISSN:1286-4579