Innate Immune Responses to Systemic Acinetobacter baumannii Infection in Mice: Neutrophils, but Not Interleukin-17, Mediate Host Resistance
Innate Immune Responses to Systemic Acinetobacter baumannii Infection in Mice: Neutrophils, but Not Interleukin-17, Mediate Host Resistance
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DOI：
10.1128/iai.00069-11
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发表时间：
2011-08-01
影响因子：
3.1
通讯作者：
Eisenstein, Toby K.
中科院分区：
文献类型：
--
作者：
Breslow, Jessica M.;Meissler, Joseph J., Jr.;Eisenstein, Toby K.
鲍曼不动杆菌是一种医院感染的病原体，具有高流行率的多重耐药菌株，可引起肺炎和败血症。目前的研究进一步开发了这种感染的全身性小鼠模型，并表征了对生物体的选定先天免疫反应。五个临床分离株，不同程度的抗生素耐药性，在两个小鼠品系，雄性和雌性小鼠之间，使用腹腔感染的毒力进行了评估。在细菌菌株之间发现了近1,000倍的毒力差异，但没有观察到性别或小鼠菌株之间的显著差异。结果发现，微生物从腹膜腔迅速传播到肺和脾，并在那里复制。观察到持续性脓毒症状态。感染进展迅速，36 - 48 h死亡。用抗Ly-6 G抗体耗竭中性粒细胞可缩短平均死亡时间并增加死亡率。白细胞介素-17（IL-17）通过诱导趋化因子角化细胞衍生的化学引诱物（KC/CXCL 1）（人IL-8的小鼠同系物）的产生来促进中性粒细胞的反应。不动杆菌感染导致IL-17和KC/CXCL 1的双相增加。使用特异性抗体，既不消耗IL-17也不消耗KC/CXCL 1，导致感染后10小时感染小鼠器官中细菌负荷的差异。IL-17 a（-/-）和野生型小鼠之间的细菌负荷的比较证实，这种细胞因子的缺乏不会使小鼠对不动杆菌感染敏感。这些研究明确表明中性粒细胞在抵抗系统性不动杆菌感染中的重要性。然而，IL-17和KC/CXCL 1都不是有效的宿主防御这种生物体全身感染所必需的。
Acinetobacter baumannii is a nosocomial pathogen with a high prevalence of multiple-drug-resistant strains, causing pneumonia and sepsis. The current studies further develop a systemic mouse model of this infection and characterize selected innate immune responses to the organism. Five clinical isolates, with various degrees of antibiotic resistance, were assessed for virulence in two mouse strains, and between male and female mice, using intraperitoneal infection. A nearly 1,000-fold difference in virulence was found between bacterial strains, but no significant differences between sexes or mouse strains were observed. It was found that microbes disseminated rapidly from the peritoneal cavity to the lung and spleen, where they replicated. A persistent septic state was observed. The infection progressed rapidly, with mortality between 36 and 48 h. Depletion of neutrophils with antibody to Ly-6G decreased mean time to death and increased mortality. Interleukin-17 (IL-17) promotes the response of neutrophils by inducing production of the chemokine keratinocyte-derived chemoattractant (KC/CXCL1), the mouse homolog of human IL-8. Acinetobacter infection resulted in biphasic increases in both IL-17 and KC/CXCL1. Depletion of neither IL-17 nor KC/CXCL1, using specific antibodies, resulted in a difference in bacterial burdens in organs of infected mice at 10 h postinfection. Comparison of bacterial burdens between IL-17a(-/-) and wild-type mice confirmed that the absence of this cytokine did not sensitize mice to Acinetobacter infection. These studies definitely demonstrate the importance of neutrophils in resistance to systemic Acinetobacter infection. However, neither IL-17 nor KC/CXCL1 alone is required for effective host defense to systemic infection with this organism.