G-CSF induction early in uropathogenic Escherichia coli infection of the urinary tract modulates host immunity.
G-CSF induction early in uropathogenic Escherichia coli infection of the urinary tract modulates host immunity.
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DOI：
10.1111/j.1462-5822.2008.01230.x
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发表时间：
2008-12
影响因子：
3.4
通讯作者：
Hultgren SJ
中科院分区：
文献类型：
--
作者：
Ingersoll MA;Kline KA;Nielsen HV;Hultgren SJ
尿路致病性大肠杆菌 (UPEC) 是约 85% 尿路感染 (UTI) 的病原体，是主要影响女性的主要健康问题。在感染期间，中性粒细胞浸润膀胱，但募集机制尚不清楚。在这里，我们研究了 UPEC 诱导的细胞因子产生在中性粒细胞募集和 UTI 进展中的作用。我们首先检查了膀胱 UPEC 感染期间细胞因子表达的动力学及其对中性粒细胞募集的贡献。我们发现 UPEC 感染诱导多种促炎细胞因子的表达，包括粒细胞集落刺激因子（G-CSF、CSF-3），此前未知这些细胞因子参与宿主对 UTI 的反应。 G-CSF 诱导中性粒细胞从骨髓迁移；这些细胞被认为对于感染期间的细菌清除至关重要。在 UPEC 感染期间中和 G-CSF 后，我们发现循环中性粒细胞减少，中性粒细胞浸润膀胱减少，矛盾的是，膀胱中的细菌负荷减少。然而，G-CSF 的消耗导致巨噬细胞激活细胞因子相应增加，例如单核细胞趋化蛋白-1（MCP-1、CCL-2）和 Il-1β，这可能是宿主对 UPEC 感染反应的关键，可能解决细菌负担减少的矛盾问题。因此，G-CSF 在 UPEC 感染期间发挥着以前未被认识的作用来调节宿主炎症反应。
Uropathogenic Escherichia coli (UPEC), the causative agent of approximately 85% of urinary tract infections (UTI), is a major health concern primarily affecting women. During infection, neutrophils infiltrate the bladder, but the mechanism of recruitment is not well understood. Here, we investigated the role of UPEC-induced cytokine production in neutrophil recruitment and UTI progression. We first examined the kinetics of cytokine expression during UPEC infection of the bladder, and their contribution to neutrophil recruitment. We found that UPEC infection induces expression of several pro-inflammatory cytokines including granulocyte colony-stimulating factor (G-CSF, CSF-3), not previously known to be involved in the host response to UTI. G-CSF induces neutrophil emigration from the bone marrow; these cells are thought to be critical for bacterial clearance during infection. Upon neutralization of G-CSF during UPEC infection, we found fewer circulating neutrophils, decreased neutrophil infiltration into the bladder and, paradoxically, a decreased bacterial burden in the bladder. However, depletion of G-CSF resulted in a corresponding increase in macrophage-activating cytokines, such as monocyte chemotactic protein-1 (MCP-1, CCL-2) and Il-1β, which may be key in host response to UPEC infection, potentially resolving the paradoxical decreased bacterial burden. Thus, G-CSF acts in a previously unrecognized role to modulate the host inflammatory response during UPEC infection.
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影响因子：
7.8
作者：
Byrne, P V;Guilbert, L J;Stanley, E R
通讯作者：
Stanley, E R
影响因子：
3.4
作者：
Bergsten, Goran;Wullt, Bjorn;Svanborg, Catharina
通讯作者：
Svanborg, Catharina
影响因子：
3.1
作者：
Billips, Benjamin K.;Forrestal, Sarah G.;Schaeffer, Anthony J.
通讯作者：
Schaeffer, Anthony J.
影响因子：
6.4
作者：
Barsig, J;Bundschuh, DS;Wendel, A
通讯作者：
Wendel, A
影响因子：
19.6
作者：
Godaly, G.;Otto, G.;Svanborg, C.
通讯作者：
Svanborg, C.