MyD88-dependent signaling influences fibrosis and alternative macrophage activation during Staphylococcus aureus biofilm infection.
MyD88-dependent signaling influences fibrosis and alternative macrophage activation during Staphylococcus aureus biofilm infection.
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DOI：
10.1371/journal.pone.0042476
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kielian T
中科院分区：
文献类型：
--
作者：
Hanke ML;Angle A;Kielian T
细菌生物膜代表了基于其逃避宿主免疫和寄生虫介导的清除的能力的显著治疗挑战。最近的研究表明，IL-1β参与了生物膜的遏制，而Toll样受体（TLR）则没有影响。这是有趣的，因为IL-1受体（IL-1 R）和大多数TLR都影响MyD 88依赖性信号通路，但这种关键的衔接子在调节宿主对生物膜生长的反应中的作用尚不清楚。因此，我们研究了S.金黄色葡萄球菌导管相关的生物膜感染在MyD 88敲除（KO）小鼠。在早期感染期间，MyD 88 KO动物在导管和周围组织上显示出显著增加的细菌负荷，与野生型（WT）小鼠相比，这与向心脏和肾脏的传播增强一致。在MyD 88 KO小鼠中，几种促炎介质（包括IL-6、IFN-γ和CXCL 1）的表达显著降低，主要是在感染的后期。有趣的是，生物膜感染组织的免疫荧光染色显示，MyD 88 KO小鼠的纤维化增加，同时交替激活的M2巨噬细胞的募集增强。在先前使用IL-1β、TLR 2和TLR 9 KO小鼠进行的研究的背景下，本报告揭示了MyD 88信号传导是生物膜形成期间调节纤维化和巨噬细胞极化的主要效应途径。总之，这些发现代表了TLR和MyD 88作用在S.金黄色葡萄球菌生物膜感染。
Bacterial biofilms represent a significant therapeutic challenge based on their ability to evade host immune and antibiotic-mediated clearance. Recent studies have implicated IL-1β in biofilm containment, whereas Toll-like receptors (TLRs) had no effect. This is intriguing, since both the IL-1 receptor (IL-1R) and most TLRs impinge on MyD88-dependent signaling pathways, yet the role of this key adaptor in modulating the host response to biofilm growth is unknown. Therefore, we examined the course of S. aureus catheter-associated biofilm infection in MyD88 knockout (KO) mice. MyD88 KO animals displayed significantly increased bacterial burdens on catheters and surrounding tissues during early infection, which coincided with enhanced dissemination to the heart and kidney compared to wild type (WT) mice. The expression of several proinflammatory mediators, including IL-6, IFN-γ, and CXCL1 was significantly reduced in MyD88 KO mice, primarily at the later stages of infection. Interestingly, immunofluorescence staining of biofilm-infected tissues revealed increased fibrosis in MyD88 KO mice concomitant with enhanced recruitment of alternatively activated M2 macrophages. Taken in the context of previous studies with IL-1β, TLR2, and TLR9 KO mice, the current report reveals that MyD88 signaling is a major effector pathway regulating fibrosis and macrophage polarization during biofilm formation. Together these findings represent a novel example of the divergence between TLR and MyD88 action in the context of S. aureus biofilm infection.
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影响因子：
2.8
作者：
Bernthal, Nicholas M.;Pribaz, Jonathan R.;Stavrakis, Alexandra I.;Billi, Fabrizio;Cho, John S.;Ramos, Romela Irene;Francis, Kevin P.;Iwakura, Yoichiro;Miller, Lloyd S.
通讯作者：
Miller, Lloyd S.
影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
DOI：
10.4049/jimmunol.0903937
发表时间：
2010-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
He X;Mekasha S;Mavrogiorgos N;Fitzgerald KA;Lien E;Ingalls RR
通讯作者：
Ingalls RR
影响因子：
5.4
作者：
Barron, Luke;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.
影响因子：
3.6
作者：
Allesen-Holm, M;Barken, KB;Tolker-Nielsen, T
通讯作者：
Tolker-Nielsen, T