Nasal-Associated Lymphoid Tissue and Olfactory Epithelium as Portals of Entry for Burkholderia pseudomallei in Murine Melioidosis
Nasal-Associated Lymphoid Tissue and Olfactory Epithelium as Portals of Entry for Burkholderia pseudomallei in Murine Melioidosis
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DOI：
10.1086/599210
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发表时间：
2009-06-15
影响因子：
6.4
通讯作者：
Beacham, Ifor R.
中科院分区：
文献类型：
--
作者：
Owen, Suzzanne J.;Batzloff, Michael;Beacham, Ifor R.
背景。假性伯克氏菌是类鼻疽病的病原体，一般认为是通过吸入环境中的灰尘或水滴而获得的。在本研究中，我们发现鼻黏膜感染可能是类鼻疽病的一个重要入口。小鼠鼻内接种后，通过生物发光成像和冠状切片免疫组织学分析监测感染情况。同时对器官和组织标本的细菌负荷进行了监测。生物发光成像显示定植和复制在鼻腔，包括鼻相关淋巴组织（NALT）。冠状切片分析和免疫荧光显微镜进一步显示呼吸道上皮和嗅觉上皮（包括相关神经束）以及NALT中存在感染。具有重要意义的是，在血液中检测到细菌之前，嗅觉上皮和大脑被迅速感染，而一个荚膜缺陷突变体感染大脑而不显著感染血液。这些数据表明，嗅觉神经是进入大脑的途径，这一途径在人类神经类鼻疽病例中可能是平行的。本研究将注意力集中在作为入口的上呼吸道上，特别关注NALT作为通过血液发生全系统感染的途径，以及嗅觉上皮作为直接进入大脑的途径。
Background. Burkholderia pseudomallei, the causative agent of melioidosis, is generally considered to be acquired via inhalation of dust or water droplets from the environment. In this study, we show that infection of the nasal mucosa is potentially an important portal of entry in melioidosis.Methods. After intranasal inoculation of mice, infection was monitored by bioluminescence imaging and by immunohistological analysis of coronal sections. The bacterial loads in organ and tissue specimens were also monitored.Results. Bioluminescence imaging showed colonization and replication in the nasal cavity, including the nasal-associated lymphoid tissue (NALT). Analysis of coronal sections and immunofluorescence microscopy further demonstrated the presence of infection in the respiratory epithelium and the olfactory epithelium (including associated nerve bundles), as well as in the NALT. Of significance, the olfactory epithelium and the brain were rapidly infected before bacteria were detected in blood, and a capsule-deficient mutant infected the brain without significantly infecting blood.Conclusions. These data suggest that the olfactory nerve is the route of entry into the brain and that this route of entry may be paralleled in cases of human neurologic melioidosis. This study focuses attention on the upper respiratory tract as a portal of entry, specifically focusing on NALT as a route for the development of systemic infection via the bloodstream and on the olfactory epithelium as a direct route to the brain.