Local Production of IFN-γ by Invariant NKT Cells Modulates Acute Lyme Carditis
Local Production of IFN-γ by Invariant NKT Cells Modulates Acute Lyme Carditis
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DOI：
10.4049/jimmunol.0804111
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发表时间：
2009-03-15
影响因子：
4.4
通讯作者：
Anguita, Juan
中科院分区：
文献类型：
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作者：
Olson, Chris M., Jr.;Bates, Tonya C.;Anguita, Juan
莱姆病伯氏疏螺旋体是唯一已知的直接激活不变NKT(INKT)细胞的人类病原体。不同品系小鼠之间iNKT细胞的数量和激活动力学有很大差异。我们现在使用C57BL/6小鼠报告iNKT细胞反应在莱姆病发病机制中的作用，C57BL/6小鼠是一种具有最佳iNKT细胞活性的菌株，它抵抗螺旋体诱导的炎症的发展。在实验感染B6小鼠期间，iNKT细胞定位于炎症的心脏，在那里它们被表达CD1d的巨噬细胞激活。体内iNKT细胞的激活导致干扰素-γ的产生，我们证明这至少通过两种机制改善了小鼠莱姆型心脏炎的严重程度。首先，干扰素-γ增强巨噬细胞对伯氏杆菌的识别，导致螺旋体吞噬功能增强。其次，巨噬细胞的干扰素-γ激活增加了CD1d的表面表达，从而促进了iNKT的进一步激活。综上所述，我们的数据表明，在耐药背景下，B6，iNKT细胞通过干扰素-γ的作用调节小鼠莱姆心肌炎的严重程度，在感染期间，干扰素-γ似乎通过正反馈循环进行自我更新。免疫学杂志，2009,182：3728-3734。
The Lyme disease spirochete Borrelia burgdorferi is the only known human pathogen that directly activates invariant NKT (iNKT) cells. The number and activation kinetics of iNKT cells vary greatly among different strains of mice. We now report the role of the iNKT cell response in the pathogenesis of Lyme disease using C57BL/6 mice, a strain with optimal iNKT cell activation that is resistant to the development of spirochetal-induced inflammation. During experimental infection of B6 mice with B. burgdorferi, iNKT cells localize to the inflamed heart where they are activated by CD1d-expressing macrophages. Activation of iNKT cells in vivo results in the production of IFN-gamma which we demonstrate ameliorates the severity of murine Lyme carditis by at least two mechanisms. First, IFN-gamma enhances the recognition of B. burgdorferi by macrophages, leading to increased phagocytosis of the spirochete. Second, IFN-gamma activation of macrophages increases the surface expression of CD1d, thereby facilitating further iNKT activation. Collectively, our data demonstrate that in the resistant background, B6, iNKT cells modulate the severity of murine Lyme carditis through the action of IFN-gamma, which appears to self-renew through a positive feedback loop during infection. The Journal of Immunology, 2009, 182: 3728-3734.