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-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.
Nakamatsu
Masashi
M
Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Yamamoto
Natsuo
N
Hatta
Masumitsu
M
Nakasone
Chikara
C
Kinjo
Takeshi
T
Miyagi
Kazuya
K
Uezu
Kaori
K
Nakamura
Kiwamu
K
Nakayama
Toshinori
T
Taniguchi
Masaru
M
Iwakura
Yoichiro
Y
Kaku
Mitsuo
M
Fujita
Jiro
J
Kawakami
Kazuyoshi
K
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018925:Chemokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma