Noto Michael J, Boyd Kelli L, Burns William J, Varga Matthew G, Peek Richard M, Skaar Eric P
Tennessee Valley Healthcare System, U.S. Department of Veterans Affairs, Nashville, Tennessee, USA Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Infect Immun. 2015 Oct;83(10):4134-41. doi: 10.1128/IAI.00410-15. Epub 2015 Aug 3.
Acinetobacter baumannii is a common nosocomial pathogen capable of causing severe diseases associated with significant morbidity and mortality in impaired hosts. Pattern recognition receptors, such as the Toll-like receptors (TLRs), play a key role in pathogen detection and function to alert the immune system to infection. Here, we examine the role for TLR9 signaling in response to A. baumannii infection. In a murine model of A. baumannii pneumonia, TLR9(-/-) mice exhibit significantly increased bacterial burdens in the lungs, increased extrapulmonary bacterial dissemination, and more severe lung pathology compared with those in wild-type mice. Following systemic A. baumannii infection, TLR9(-/-) mice have significantly increased bacterial burdens in the lungs, as well as decreased proinflammatory cytokine and chemokine production. These results demonstrate that TLR9-mediated pathogen detection is important for host defense against the opportunistic pathogen Acinetobacter baumannii.
鲍曼不动杆菌是一种常见的医院病原体,能够在受损宿主中引发与高发病率和死亡率相关的严重疾病。模式识别受体,如Toll样受体(TLR),在病原体检测中起关键作用,并能提醒免疫系统感染的存在。在此,我们研究了TLR9信号在应对鲍曼不动杆菌感染时的作用。在鲍曼不动杆菌肺炎的小鼠模型中,与野生型小鼠相比,TLR9基因敲除(-/-)小鼠肺部的细菌载量显著增加,肺外细菌播散增加,肺部病理改变更严重。在全身性鲍曼不动杆菌感染后,TLR9(-/-)小鼠肺部的细菌载量显著增加,同时促炎细胞因子和趋化因子的产生减少。这些结果表明,TLR9介导的病原体检测对于宿主抵御机会性病原体鲍曼不动杆菌至关重要。