Francisella tularensis live vaccine strain induces macrophage alternative activation as a survival mechanism.
Francisella tularensis live vaccine strain induces macrophage alternative activation as a survival mechanism.
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DOI：
10.4049/jimmunol.181.6.4159
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发表时间：
2008-09-15
期刊：
影响因子：
--
通讯作者：
Vogel SN
中科院分区：
文献类型：
--
作者：
Shirey KA;Cole LE;Keegan AD;Vogel SN
土拉热弗朗西丝菌（Ft）是土拉菌病的病原体，在感染早期引起强烈的炎症反应，但在宿主巨噬细胞内持续存在，如果不加以控制，可能是致命的。我们在此报告，Ft活疫苗株（LVS）感染的小鼠巨噬细胞诱导TLR 2依赖性表达的“替代激活”标志物，随后出现的“经典激活”标志物。Ft LVS腹腔感染也可诱导选择性激活的巨噬细胞（AA-Mφ）。用rIL-4处理细胞或用Ft LVS感染细胞诱导AA-Mφ可促进细胞内Ft的复制，这与经典活化的（IFN-γ + LPS）巨噬细胞促进细胞内Ft LVS的杀伤相反。Ft LVS未能诱导IL-4 R α−/−或STAT 6 −/−巨噬细胞的替代激活，并延长了这些细胞中的经典炎症反应，导致Ft的细胞内杀伤。用抗IL-4和抗IL-13抗体处理巨噬细胞可减弱Ft诱导的AA-Mφ分化，并导致IL-12 p70表达增加和细菌复制减少。在体内，与WT小鼠相比，Ft感染的IL-4 R α−/−小鼠的存活率增加。因此，通过Ft LVS将巨噬细胞分化从经典活化状态重定向到替代活化状态使得生物体能够以宿主为代价存活。
Francisella tularensis(Ft), the causative agent of tularemia, elicits a potent inflammatory response early in infection, yet persists within host macrophages and can be lethal if left unchecked. We report herein that Ft live vaccine strain (LVS) infection of murine macrophages induced TLR2-dependent expression of “alternative activation” markers that followed the appearance of “classically activated” markers. Intraperitoneal infection with Ft LVS also resulted in induction of alternatively activated macrophages (AA-Mφ). Induction of AA-Mφ by treatment of cells with rIL-4 or by infection with Ft LVS promoted replication of intracellular Ft, in contrast to classically activated (IFN-γ + LPS) macrophages that promoted intracellular killing of Ft LVS. Ft LVS failed to induce alternative activation in IL-4Rα−/− or STAT6−/− macrophages and prolonged the classical inflammatory response in these cells, resulting in intracellular killing of Ft. Treatment of macrophages with anti-IL-4 and anti-IL-13 antibody blunted Ft-induced AA-Mφ differentiation and resulted in increased expression of IL-12 p70 and decreased bacterial replication. In vivo, Ft-infected IL-4Rα−/− mice exhibited increased survival compared to WT mice. Thus, redirection of macrophage differentiation by Ft LVS from a classical to an alternative activation state enables the organism to survive at the expense of the host.
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影响因子：
3.1
作者：
Cole, Leah E.;Shirey, Kari Ann;Vogel, Stefanie N.
通讯作者：
Vogel, Stefanie N.
影响因子：
3.1
作者：
Dreisbach, VC;Cowley, S;Elkins, KL
通讯作者：
Elkins, KL
影响因子：
14.2
作者：
Hogan, Simon P.;Seidu, Luqman;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
9.3
作者：
Colton CA;Mott RT;Sharpe H;Xu Q;Van Nostrand WE;Vitek MP
通讯作者：
Vitek MP
I型干扰素信号在弗朗西斯拉感染过程中激活炎症体需要。
影响因子：
15.3
作者：
Henry, Thomas;Brotcke, Anna;Weiss, David S.;Thompson, Lucinda J.;Monack, Denise M.
通讯作者：
Monack, Denise M.