CXCL1 regulates pulmonary host defense to Klebsiella Infection via CXCL2, CXCL5, NF-kappaB, and MAPKs.
CXCL1 regulates pulmonary host defense to Klebsiella Infection via CXCL2, CXCL5, NF-kappaB, and MAPKs.
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DOI：
10.4049/jimmunol.0903843
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发表时间：
2010-11-15
期刊：
影响因子：
--
通讯作者：
Jeyaseelan S
中科院分区：
文献类型：
--
作者：
Cai S;Batra S;Lira SA;Kolls JK;Jeyaseelan S
肺部细菌感染是导致死亡的主要原因。自从抗生素问世以来，耐多药肺炎克雷伯氏菌(KP)成为一个日益严重的威胁。因此，开发加强抗菌防御的方法是必要的。中性粒细胞募集是清除细菌的关键，中性粒细胞在肺内的迁移需要产生ELR+CXC趋化因子。尽管肺特异性CXCL1/KC转基因表达可导致中性粒细胞介导的KP清除，但KC介导的宿主防御KP的机制尚不清楚。在这里，我们用KC-/-小鼠描述了KC在肺部KP感染过程中的宿主防御功能。我们的研究结果表明，KC对肺组织中CXCL2/MIP-2和CXCL5/LIX的表达以及对NF-κB和MAPKs的激活具有重要作用。此外，来源于造血细胞和常驻细胞的KC有助于宿主对KP的防御。在KP感染之前，小鼠的中性粒细胞耗尽表明，肺中MIP-2和Lix的产生没有差异，或者NF-κB和MAPKs的激活没有差异。利用小鼠骨髓和肺泡巨噬细胞，我们证实了KC在KP感染时上调了MIP-2，并激活了NF-κB和MAPK。此外，在KP攻击之前中和BMMS中的KC可以减少细菌诱导的KC、MIP-2的产生以及NF-κB和MAPK的激活。这些发现揭示了造血细胞和常驻细胞产生的KC通过激活转录因子和MAPK以及细胞黏附分子和其他中性粒细胞趋化因子的表达，在调节肺宿主对细菌病原体的防御中的重要性。
Pulmonary bacterial infections are a leading cause of death. Since the introduction of antibiotics, multidrug-resistant Klebsiella pneumoniae (Kp) became an escalating threat. Therefore, development of methods to augment antibacterial defense is warranted. Neutrophil recruitment is critical to clear bacteria and neutrophil migration in the lung requires the production of ELR+ CXC chemokines. Although lung specific CXCL1/KC transgene expression causes neutrophil-mediated clearance of Kp, the mechanisms underlying KC-mediated host defense against Kp have not been explored. Here we delineated the host defense functions of KC during pulmonary Kp infection using KC-/- mice. Our findings demonstrate that KC is important for expression of CXCL2/MIP-2 and CXCL5/LIX and activation of NF-κB, and MAPKs in the lung. Furthermore, KC-derived from both hematopoietic and resident cells contributes to host defense against Kp. Neutrophil depletion in mice prior to Kp infection reveals no differences in the production of MIP-2 and LIX or activation of NF-κB and MAPKs in the lung. Using murine bone marrow-derived (BMMs) and alveolar macrophages, we confirmed KC-mediated upregulation of MIP-2 and activation of NF-κB and MAPKs upon Kp infection. Moreover, neutralizing KC in BMMs prior to Kp challenge decreases bacteria-induced production of KC, MIP-2 and activation of NF-κB and MAPKs. These findings reveal the importance of KC produced by hematopoietic and resident cells in regulating pulmonary host defense against a bacterial pathogen via the activation of transcription factors and MAPKs as well as the expression of cell adhesion molecules and other neutrophil chemoattractants.
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DOI：
10.1165/rcmb.2008-0152oc
发表时间：
2009-06-01
影响因子：
6.4
作者：
Cai, Shanshan;Zemans, Rachel L.;Jeyaseelan, Samithamby
通讯作者：
Jeyaseelan, Samithamby
影响因子：
4.4
作者：
Jeyaseelan, Samithamby;Young, Scott K.;Worthen, G. Scott
通讯作者：
Worthen, G. Scott
影响因子：
8.8
作者：
Abraham, E
通讯作者：
Abraham, E
影响因子：
4.4
作者：
Nagatani, K;Dohi, M;Yamamoto, K
通讯作者：
Yamamoto, K
影响因子：
4.4
作者：
Jeyaseelan, Samithamby;Young, Scott K.;Worthen, G. Scott
通讯作者：
Worthen, G. Scott