Role of neutrophils and NADPH phagocyte oxidase in host defense against respiratory infection with virulent Francisella tularensis in mice

Role of neutrophils and NADPH phagocyte oxidase in host defense against respiratory infection with virulent Francisella tularensis in mice
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DOI:
10.1016/j.micinf.2011.01.010
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发表时间:
2011-05-01
影响因子:
5.8
通讯作者:
Chen, Wangxue
Chen, Wangxue
中科院分区:
医学3区
文献类型:
--
作者:
KuoLee, Rhonda;Harris, Greg;Chen, Wangxue

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土拉热弗朗西斯菌亚种(亚种)土拉热是CDC A类生物战剂,吸入少至15个杆菌即可引发严重疾病。相对较少的是知道宿主防御的细胞和分子机制,对呼吸道感染的亚属。土拉热。在这项研究中,我们研究了中性粒细胞和NADPH吞噬细胞氧化酶在小鼠鼻内感染模型中宿主抵抗肺部感染的作用。我们发现,尽管中性粒细胞招募到肺部和增加浓度的嗜中性粒细胞趋化因子(KC,MIP-2和RANTES)的支气管肺泡灌洗液后,鼻内接种的病原体,无论是消耗中性粒细胞,也没有增强其招募到肺部细菌负荷或生存率/时间有任何影响。然而,NADPH吞噬细胞氧化酶(gp 91(phox-/-))缺陷的小鼠确实表现出更高的组织和血液细菌负荷,并死于感染比野生型C57 BL/6小鼠早一天。这些结果表明,虽然中性粒细胞不是主要的效应细胞防御亚群。土拉菌感染时,NADPH吞噬细胞氧化酶确实起边缘作用。Crown Copyright(C)2011由Elsevier Masson SAS代表巴斯德研究所发布。All rights reserved.
Francisella tularensis subspecies (subsp.) tularensis is a CDC Category A biological warfare agent and inhalation of as few as 15 bacilli can initiate severe disease. Relatively little is known about the cellular and molecular mechanisms of host defense against respiratory infection with subsp. tularensis. In this study, we examined the role of neutrophils and NADPH phagocyte oxidase in host resistance to pulmonary infection in a mouse intranasal infection model. We found that despite neutrophil recruitment to the lungs and increased concentrations of neutrophil-chemotactic chemokines (KC, MIP-2 and RANTES) in the bronchoalveolar lavage fluid following intranasal inoculation of the pathogen, neither depletion of neutrophils nor enhancement of their recruitment into the lungs had any impact on bacterial burdens or survival rate/time. Nevertheless, mice deficient in NADPH phagocyte oxidase (gp91(phox-/-)) did exhibit higher tissue and blood bacterial burdens and succumbed to infection one day earlier than wild-type C57BL/6 mice. These results imply that although neutrophils are not a major effector cell in defense against subsp. tularensis infection, NADPH phagocyte oxidase does play a marginal role. Crown Copyright (C) 2011 Published by Elsevier Masson SAS on behalf of Institut Pasteur. All rights reserved.