A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei
A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei
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DOI：
10.1086/509810
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发表时间：
2007-01-01
影响因子：
6.4
通讯作者：
Bancroft, Gregory J.
中科院分区：
文献类型：
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作者：
Easton, Anna;Haque, Ashraful;Bancroft, Gregory J.
吸入是类鼻疽伯克霍尔德氏菌感染的重要途径，类鼻疽的病原体。在耐药C57 BL/6小鼠中，鼻内B给药后，活化的中性粒细胞迅速聚集到肺部。类鼻疽感染。通过使用抗Gr-1（+）细胞耗竭性单克隆抗体RB 6 - 8 C5来预防这种反应会严重加重疾病，导致与4天内肺细菌负荷增加1000倍相关的急性致死性感染。C57 BL/6干扰素（IFN）-γ（-/-）小鼠也对肺B急性易感。感染，在攻击后3天内死亡;这表明IFN-γ对于肺中的控制是必不可少的，并且先于中性粒细胞在抵抗中的保护作用。在嗜中性粒细胞耗竭的小鼠中，肿瘤坏死因子（TNF）-α、IFN-γ和白细胞介素-6的肺浓度降低高达98%。自然杀伤细胞是IFN-γ的主要来源，单核细胞是TNF-α的主要来源，这表明中性粒细胞在肺中早期细胞因子环境的产生中起重要的间接作用。
Inhalation is an important route of infection with Burkholderia pseudomallei, the causative agent of melioidosis. In resistant C57BL/6 mice, activated neutrophils are rapidly recruited to the lungs after intranasal B. pseudomallei infection. Prevention of this response by use of the anti-Gr-1(+) cell-depleting monoclonal antibody RB6-8C5 severely exacerbated disease, resulting in an acute lethal infection associated with a 1000-fold increase in lung bacterial loads within 4 days. C57BL/6 interferon (IFN)-gamma(-/-) mice were also acutely susceptible to pulmonary B. pseudomallei infection, dying within 3 days of challenge; this suggests that IFN-gamma is essential for control in the lungs and precedes the protective role of neutrophils in resistance. In neutrophil-depleted mice, lung concentrations of tumor necrosis factor (TNF)-alpha, IFN-gamma, and interleukin-6 were decreased by up to 98%. Natural killer cells were the principle source of IFN-gamma, and monocytes were the principle source of TNF-alpha, suggesting that neutrophils play an important indirect role in the generation of the early cytokine environment in the lungs.