Forkhead Box O1 Regulates Macrophage Polarization Following Staphylococcus aureus Infection: Experimental Murine Data and Review of the Literature.
Forkhead Box O1 Regulates Macrophage Polarization Following Staphylococcus aureus Infection: Experimental Murine Data and Review of the Literature.
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Forkhead Box O1 在金黄色葡萄球菌感染后调节巨噬细胞极化：实验鼠数据和文献综述。
DOI：
10.1007/s12016-016-8531-1
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发表时间：
2016
影响因子：
9.1
通讯作者：
Lian Zhe-Xiong
中科院分区：
文献类型：
--
作者：
Wang Yu-Chen;Ma Hong-Di;Yin Xue-Ying;Wang Yin-Hu;Liu Qing-Zhi;Yang Jing-Bo;Shi Qing-Hua;Sun Baolin;Gershwin M Eric;Lian Zhe-Xiong
巨噬细胞的功能导致有效的宿主反应对抵抗金黄色葡萄球菌的保护至关重要。tissue-invadingS深处。最初被巨噬细胞对抗的金黄色葡萄球菌通过表面受体，尤其是toll样受体2 (TLR2)，触发巨噬细胞聚集，诱导炎症反应。在这里，我们发现巨噬细胞在感染期间在肝脏中形成散发性聚集体。在这些聚集体中，巨噬细胞与T细胞共定位，并且对于T细胞的浸润是必不可少的。此外，我们还关注了叉头盒转录因子O1 （FoxO1）条件敲除lyscre /+FoxO1fl/flmice后巨噬细胞极化的机制。本文报道巨噬细胞通过TLR2的M1-M2极化是由FoxO1内在调节的。事实上，为了使fox01活性有效，刺激TLR2是必不可少的。然而,追随者。巨噬细胞FoxO1表达减少，由于tlr2介导的PI3K/Akt和c-Raf/MEK/ERK通路的激活，FoxO1磷酸化增加。在lyscre /+FoxO1fl/flmice感染后，小鼠变得更容易感染toS。肝内巨噬细胞聚集减少，Th1和Th17反应减弱。FoxO1的废除减少了ys引发的M1促炎反应。巨噬细胞M2极化增强。相比之下，巨噬细胞中FoxO1的过表达增加了促炎介质和功能性表面分子的表达。综上所述，巨噬细胞FoxO1对促进M1极化和维持T细胞免疫应答至关重要。肝脏金黄色菌感染。FoxO1通过磷酸化动态调控TLR2下游巨噬细胞M1-M2极化。
The functions of macrophages that lead to effective host responses are critical for protection againstStaphylococcus aureus. Deep tissue-invadingS. aureusinitially countered by macrophages trigger macrophage accumulation and induce inflammatory responses through surface receptors, especially toll-like receptor 2 (TLR2). Here, we found that macrophages formed sporadic aggregates in the liver during infection. Within those aggregates, macrophages co-localized with T cells and were indispensable for their infiltration. In addition, we have focused on the mechanisms underlying the polarization of macrophages in Forkhead box transcription factor O1 (FoxO1) conditional knockoutLysCre/+FoxO1fl/flmice followingS. aureusinfection and report herein that macrophage M1-M2 polarization via TLR2 is intrinsically regulated by FoxO1. Indeed, for effective FoxO1 activity, stimulation of TLR2 is essential. However, followingS. aureuschallenge, there was a decrease in macrophage FoxO1, with increased phosphorylation of FoxO1 because of TLR2-mediated activation of PI3K/Akt and c-Raf/MEK/ERK pathway. Following infection inLysCre/+FoxO1fl/flmice, mice became more susceptible toS. aureuswith reduced macrophage aggregation in the liver and attenuated Th1 and Th17 responses. FoxO1 abrogation reduced M1 pro-inflammatory responses triggered byS. aureusand enhanced M2 polarization in macrophages. In contrast, overexpression of FoxO1 in macrophages increased pro-inflammatory mediators and functional surface molecule expression. In conclusion, macrophage FoxO1 is critical to promote M1 polarization and maintain a competent T cell immune response againstS. aureusinfection in the liver. FoxO1 regulates macrophage M1-M2 polarization downstream of TLR2 dynamically through phosphorylation.