Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense.
Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense.
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DOI：
10.1084/jem.194.4.519
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发表时间：
2001-08-20
期刊：
影响因子：
--
通讯作者：
Kolls JK
中科院分区：
文献类型：
--
作者：
Ye P;Rodriguez FH;Kanaly S;Stocking KL;Schurr J;Schwarzenberger P;Oliver P;Huang W;Zhang P;Zhang J;Shellito JE;Bagby GJ;Nelson S;Charrier K;Peschon JJ;Kolls JK
细菌性肺炎是HIV感染的一种日益严重的并发症，与CD 4+淋巴细胞计数呈负相关。白细胞介素（IL）-17是主要由CD 4 + T细胞产生的细胞因子，其通过粒细胞集落刺激因子（G-CSF）的产生诱导粒细胞生成并诱导CXC趋化因子。我们假设IL-17受体（IL-17 R）信号传导对于G-CSF和CXC趋化因子的产生和肺宿主防御是至关重要的。为了验证这一点，我们使用了一个肺炎克雷伯氏菌肺部感染模型，在小鼠中遗传缺陷的IL-17 R或在小鼠中过表达可溶性IL-17 R。IL-17 R缺陷小鼠对鼻内K.在48小时后，肺炎患者的死亡率为100%，而对照组的死亡率仅为40%。IL-17 R基因敲除（KO）小鼠在中性粒细胞募集到肺泡腔中的过程中表现出明显的延迟，并且具有更大的K.与对照小鼠相比，这一缺陷与K.在IL-17 R KO小鼠中进行肺炎链球菌攻击。因此，IL-17 R信号传导对于G-CSF和MIP-2的最佳产生以及肺K的局部控制是至关重要的。肺炎感染。这些数据支持受损的IL-17 R信号传导作为CD 4淋巴细胞缺乏易患细菌性肺炎的潜在机制。
Bacterial pneumonia is an increasing complication of HIV infection and inversely correlates with the CD4+ lymphocyte count. Interleukin (IL)-17 is a cytokine produced principally by CD4+ T cells, which induces granulopoiesis via granulocyte colony-stimulating factor (G-CSF) production and induces CXC chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokine production and lung host defenses. To test this, we used a model of Klebsiella pneumoniae lung infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R–deficient mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO) mice displayed a significant delay in neutrophil recruitment into the alveolar space, and had greater dissemination of K. pneumoniae compared with control mice. This defect was associated with a significant reduction in steady-state levels of G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling is critical for optimal production of G-CSF and MIP-2 and local control of pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.
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影响因子：
4.4
作者：
Schwarzenberger, P;Huang, WT;Kolls, JK
通讯作者：
Kolls, JK
影响因子：
32.4
作者：
Yao, ZB;Fanslow, WC;Spriggs, MK
通讯作者：
Spriggs, MK
DOI：
10.1084/jem.183.6.2593
发表时间：
1996-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fossiez F;Djossou O;Chomarat P;Flores-Romo L;Ait-Yahia S;Maat C;Pin JJ;Garrone P;Garcia E;Saeland S;Blanchard D;Gaillard C;Das Mahapatra B;Rouvier E;Golstein P;Banchereau J;Lebecque S
通讯作者：
Lebecque S
DOI：
10.1073/pnas.91.1.215
发表时间：
1994-01-04
影响因子：
11.1
作者：
KOLLS, J;PEPPEL, K;BEUTLER, B
通讯作者：
BEUTLER, B
影响因子：
9.6
作者：
Nelson, S
通讯作者：
Nelson, S