Autophagy enhances bacterial clearance during P. aeruginosa lung infection.
Autophagy enhances bacterial clearance during P. aeruginosa lung infection.
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DOI：
10.1371/journal.pone.0072263
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lin TJ
中科院分区：
文献类型：
--
作者：
Junkins RD;Shen A;Rosen K;McCormick C;Lin TJ
铜绿假单胞菌是一种机会性细菌病原体，是囊性纤维化患者发病和死亡的主要原因。虽然铜绿假单胞菌主要被认为是一种细胞外病原体，但最近的报道表明，在整个感染过程中，这种细菌获得了进入并居住在宿主细胞内的能力。正常情况下，细胞内的病原体会通过一种叫做自噬的过程被清除，这种过程会隔离和降解部分细胞质，包括入侵的细菌。然而，自噬在宿主体内防御铜绿假单胞菌中的作用尚不清楚。了解自噬在铜绿假单胞菌感染中的作用是特别重要的，因为导致囊性纤维化的突变最近被证明会导致自噬途径的阻断，这可能会增加对感染的易感性。在这里，我们证明了铜绿假单胞菌诱导肥大细胞自噬，肥大细胞被认为是宿主防御细菌感染的哨兵。我们进一步证明，通过药物手段或蛋白敲低抑制细胞内铜绿假单胞菌的体外清除，而药物诱导自噬显著增加细菌清除。最后，我们发现体内自噬的药理学操作可以有效地调节细菌对肺内铜绿假单胞菌的清除。总之，我们的研究结果表明，自噬是体内针对铜绿假单胞菌感染的有效免疫应答所必需的，并且表明针对自噬途径的药物干预在铜绿假单胞菌肺部感染的治疗中具有相当大的治疗潜力。
Pseudomonas aeruginosa is an opportunistic bacterial pathogen which is the leading cause of morbidity and mortality among cystic fibrosis patients. Although P. aeruginosa is primarily considered an extacellular pathogen, recent reports have demonstrated that throughout the course of infection the bacterium acquires the ability to enter and reside within host cells. Normally intracellular pathogens are cleared through a process called autophagy which sequesters and degrades portions of the cytosol, including invading bacteria. However the role of autophagy in host defense against P. aeruginosa in vivo remains unknown. Understanding the role of autophagy during P. aeruginosa infection is of particular importance as mutations leading to cystic fibrosis have recently been shown to cause a blockade in the autophagy pathway, which could increase susceptibility to infection. Here we demonstrate that P. aeruginosa induces autophagy in mast cells, which have been recognized as sentinels in the host defense against bacterial infection. We further demonstrate that inhibition of autophagy through pharmacological means or protein knockdown inhibits clearance of intracellular P. aeruginosa in vitro, while pharmacologic induction of autophagy significantly increased bacterial clearance. Finally we find that pharmacological manipulation of autophagy in vivo effectively regulates bacterial clearance of P. aeruginosa from the lung. Together our results demonstrate that autophagy is required for an effective immune response against P. aeruginosa infection in vivo, and suggest that pharmacological interventions targeting the autophagy pathway could have considerable therapeutic potential in the treatment of P. aeruginosa lung infection.
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影响因子：
3.1
作者：
Kooguchi, K;Hashimoto, S;Sawa, T
通讯作者：
Sawa, T
DOI：
10.1007/s10096-011-1530-5
发表时间：
2012-08-01
影响因子：
4.5
作者：
Le, B. V.;Khorsi-Cauet, H.;Gay-Queheillard, J.
通讯作者：
Gay-Queheillard, J.
影响因子：
13.3
作者：
Gao, Wentao;Ding, Wen-Xing;Yin, Xiao-Ming
通讯作者：
Yin, Xiao-Ming
影响因子：
3.2
作者：
Faulkner, G;Garduño, RA
通讯作者：
Garduño, RA
影响因子：
3.5
作者：
Hosokawa, Nao;Hara, Yukichi;Mizushima, Noboru
通讯作者：
Mizushima, Noboru