Mycobacterium bovis bacilli Calmette-Guerin regulates leukocyte recruitment by modulating alveolar inflammatory responses.
Mycobacterium bovis bacilli Calmette-Guerin regulates leukocyte recruitment by modulating alveolar inflammatory responses.
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DOI：
10.1177/1753425911426591
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发表时间：
2012-06
期刊：
影响因子：
3.2
通讯作者：
Godaly G
中科院分区：
文献类型：
--
作者：
Andersson M;Lutay N;Hallgren O;Westergren-Thorsson G;Svensson M;Godaly G
白细胞向上皮腔内迁移是分枝杆菌感染活跃期的一个重要特征。在本研究中，我们使用Transwell模型研究了分枝杆菌诱导白细胞募集的机制，并研究了TLR2和TLR4在这一过程中的作用。上皮细胞感染导致中性粒细胞趋化CXCL8和IL-6分泌显著增加，而单核细胞趋化CCL2和TNF-α未见分泌。与上皮反应相反，分枝杆菌感染的中性粒细胞和单核细胞分泌所有这些细胞因子。与上皮细胞因子反应相对应，分枝杆菌感染上皮细胞增加了中性粒细胞浸润，但减少了单核细胞募集。然而，单核细胞向分枝杆菌感染上皮细胞的募集在加入中性粒细胞预处理培养基后显著增加。通过流式细胞术、Western blotting和共聚焦显微镜观察发现，分枝杆菌感染也会增加肺泡上皮细胞TLR2的表达，但不会增加TLR4的表达。阻断TLR2抑制中性粒细胞募集和细胞因子分泌，而阻断TLR4的作用较小。总之，我们发现原代肺泡上皮细胞在分枝杆菌感染时产生选择性的tlr2依赖性细胞因子分泌。此外，我们发现先天免疫细胞之间的合作是建立适当的抗菌防御所必需的。
Leukocyte migration into the epithelial compartment is an important feature in the active phase of mycobacterial infections. In this study, we used the Transwell model to investigate the mechanisms behind mycobacteria-induced leukocyte recruitment and investigated the role of TLR2 and TLR4 in this process. Infection of epithelial cells resulted in significantly increased secretion of the neutrophil chemotactic CXCL8 and IL-6, but no secretion of monocyte chemotactic CCL2 or TNF-α was observed. In contrast to epithelial response, mycobacteria-infected neutrophils and monocytes secreted all these cytokines. Corresponding with epithelial cytokine response, mycobacterial infection of the epithelial cells increased neutrophil diapedesis, but decreased monocyte recruitment. However, monocyte recruitment towards mycobacteria infected epithelial cells significantly increased following addition of neutrophil pre-conditioned medium. Mycobacterial infection also increases alveolar epithelial expression of TLR2, but not TLR4, as analyzed by flow cytometry, Western blotting and visualized by confocal microscopy. Blocking of TLR2 inhibited neutrophil recruitment and cytokine secretion, while blocking of TLR4 had a lesser effect. To summarize, we found that primary alveolar epithelial cells produced a selective TLR2-dependent cytokine secretion upon mycobacterial infection. Furthermore, we found that cooperation between cells of the innate immunity is required in mounting proper antimicrobial defence.
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影响因子：
6.4
作者：
Kipnis, A;Basaraba, RJ;Cooper, AM
通讯作者：
Cooper, AM
影响因子：
56.9
作者：
Brightbill, HD;Libraty, DH;Modlin, RL
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Modlin, RL
影响因子：
82.9
作者：
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影响因子：
5.5
作者：
Heldwein, KA;Liang, MD;Fenton, MJ
通讯作者：
Fenton, MJ
影响因子：
3.1
作者：
Meddows-Taylor, S;Martin, DJ;Tiemessen, CT
通讯作者：
Tiemessen, CT