Shannon Jeffrey G, Heinzen Robert A
Coxiella Pathogenesis Section, Laboratory of Interacellular Parasites, Rocky Mountain Laboratoties, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Methods Mol Biol. 2008;431:189-200. doi: 10.1007/978-1-60327-032-8_15.
Coxiella burnetii, the agent of Q fever, is an obligate intracellular bacterium that has a tropism for cells of the mononuclear phagocyte system. Following internalization, C. burnetii remains in a phagosome that ultimately matures into a vacuole with lysosomal characteristics that supports pathogen replication. Most in vitro investigations of Coxiella - macrophage interactions have employed continuous cell lines. Although these studies have been informative, genetic alterations of immortalized cells may result in attenuated biological responses to infection relative to primary cells. Consequently, primary macrophages are preferred as in vitro model systems. Here, we describe procedures for propagation and isolation of C. burnetii from cell culture and the use of these preparations to infect primary macrophages derived from human peripheral blood monocytes. Both virulent phase I and avirulent phase II C. burnetii productively infect human monocyte-derived macrophages (MDMs) and replicate with approximately the same kinetics, thereby providing a more physiologically relevant in vitro model system to study the infectious process of this pathogen.
Q热病原体贝氏柯克斯体是一种专性细胞内细菌,对单核吞噬细胞系统的细胞具有嗜性。内化后,贝氏柯克斯体保留在吞噬体中,该吞噬体最终成熟为具有溶酶体特征的液泡,支持病原体复制。大多数关于柯克斯体与巨噬细胞相互作用的体外研究都使用了连续细胞系。尽管这些研究提供了信息,但永生化细胞的基因改变可能导致相对于原代细胞对感染的生物学反应减弱。因此,原代巨噬细胞更适合作为体外模型系统。在这里,我们描述了从细胞培养物中繁殖和分离贝氏柯克斯体的程序,以及使用这些制剂感染源自人外周血单核细胞的原代巨噬细胞的方法。强毒株I期和无毒株II期贝氏柯克斯体均能有效感染人单核细胞衍生的巨噬细胞(MDM),并以大致相同的动力学进行复制,从而提供了一个更具生理相关性的体外模型系统来研究该病原体的感染过程。