Apidianakis Yiorgos, Mindrinos Michael N, Xiao Wenzhong, Tegos George P, Papisov Michail I, Hamblin Michael R, Davis Ronald W, Tompkins Ronald G, Rahme Laurence G
Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2007 Dec 26;2(12):e1356. doi: 10.1371/journal.pone.0001356.
Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.
尽管我们对创伤病理生理学的理解最近取得了进展，但创伤患者易感染的基础仍不清楚。利用果蝇/铜绿假单胞菌损伤和感染模型来鉴定导致严重创伤后易感染的宿主遗传成分。我们发现，铜绿假单胞菌会损害损伤部位的骨骼肌基因（SMG）表达，以促进感染。我们证明，SMG结构成分的激活受cJun氨基末端激酶（JNK）激酶Hemipterous（Hep）的控制，该途径的激活促进果蝇和小鼠对铜绿假单胞菌的局部抗性。我们的研究将SMG表达和功能与易感染性增加联系起来，并表明铜绿假单胞菌通过限制受伤骨骼肌组织中的SMG表达来局部影响SMG稳态。局部增强这些宿主反应和/或抑制其被毒性铜绿假单胞菌细胞抑制，可能会带来预防或治疗严重受伤个体中有害及潜在致命感染的新疗法。
