Role of interferon-γ in Vα14+ natural killer T cell-mediated host defense against Streptococcus pneumoniae infection in murine lungsq
Role of interferon-γ in Vα14+ natural killer T cell-mediated host defense against Streptococcus pneumoniae infection in murine lungsq
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DOI：
10.1016/j.micinf.2006.12.003
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发表时间：
2007-03-01
影响因子：
5.8
通讯作者：
Kawakami, Kazuyoshi
中科院分区：
文献类型：
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作者：
Nakamatsu, Masashi;Yamamoto, Natsuo;Kawakami, Kazuyoshi
先前，我们证明V α 14+ NKT细胞和IFN-γ是嗜中性粒细胞介导的宿主防御肺炎链球菌感染的重要上游组分。在本研究中，我们通过阐明IFN-γ在V α 14+ NKT细胞促进过程中的作用来扩展这些发现。与野生型（WT）小鼠相比，向J alpha 18 KO小鼠给予重组IFN-γ可延长缩短的生存期，促进细菌的减毒清除，并改善肺部中性粒细胞积聚以及MIP-2和TNF-α合成的减少。此外，将肝单核细胞（LMNC）从WT小鼠静脉内转移至J α 18 KO小鼠中导致上述耗竭应答完全恢复，而从IFN-γ KO或J α 18 KO小鼠获得LMNC时未检测到此类效应。通过α-半乳糖神经酰胺（α-GalCer）激活V α 14+ NKT细胞显著增强了感染肺中细菌的清除、中性粒细胞的蓄积以及MIP-2和TNF-α的合成;中和抗IFN-γ抗体显著抑制了该效应。最后，在流式细胞术分析中，TNF-α的合成主要由感染肺中的CD 11b（亮+）细胞检测到。我们的研究结果表明，IFN-γ在V α 14+ NKT细胞促进的嗜中性粒细胞介导的针对肺炎球菌感染的宿主保护性应答中起重要作用。(c)2007年，Elsevier Masson SAS。All rights reserved.
Previously, we demonstrated that V alpha 14+ 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 V alpha 14+ NKT cell-promoted process. Administration of recombinant IFN-gamma to J alpha 18KO 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 J alpha 18KO mice resulted in complete recovery of the depleted responses listed above, whereas such effects were not detected when LMNC were obtained from IFN-gamma KO or J alpha 18KO mice. Activation of V alpha 14+ 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 V alpha 14+ NKT cells. (c) 2007 Elsevier Masson SAS. All rights reserved.