Macrophages from mice with the restrictive Lgn1 allele exhibit multifactorial resistance to Legionella pneumophila
Macrophages from mice with the restrictive Lgn1 allele exhibit multifactorial resistance to Legionella pneumophila
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DOI：
10.1128/iai.72.11.6221-6229.2004
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发表时间：
2004-11-01
影响因子：
3.1
通讯作者：
Isberg, RR
中科院分区：
文献类型：
--
作者：
Derré, I;Isberg, RR
虽然嗜肺军团菌可以在来自各种物种的不同细胞类型中繁殖，但大多数近交系小鼠品系的巨噬细胞不允许细胞内复制，并且几乎不允许细菌生长。这种现象可能是由位于Lgn 1基因座内的小鼠naip 5（birc 1 e）基因遗传控制的。本研究观察了C57 BL/6 J巨噬细胞对L.通过检查细菌和受感染细胞的命运，与来自容许A/J菌株的巨噬细胞中的命运相比，来确定嗜肺菌感染。我们的研究结果表明，虽然贩运的L。尽管在C57 BL/6 J巨噬细胞中含有嗜肺菌的空泡被部分破坏，但这不能解释在该菌株中观察到的细胞内生长缺陷的严重性。感染的巨噬细胞在感染后不久丢失，并且在稍后的时间，其中L.与来自A/J小鼠的那些相比，嗜肺细胞经历复制的那些是凋亡的。最后，在第一轮生长后发生细菌计数的损失。因此，C57 BL/6 J巨噬细胞对L.嗜肺菌感染似乎是多因素的，我们讨论了如何早期和晚期反应的结果，清除感染。
Although Legionella pneumophila can multiply in diverse cell types from a variety of species, macrophages from most inbred mouse strains are nonpermissive for intracellular replication and allow little or no growth of the bacteria. This phenomenon is likely genetically controlled by the mouse naip5 (birc1e) gene located within the Lgn1 locus. In this study, we have investigated the resistance of C57BL/6J macrophages to L. pneumophila infection by examining the fate of both the bacterium and the infected cells compared to that in macrophages from the permissive A/J strain. Our results indicate that although the trafficking of the L. pneumophila-containing vacuole is partially disrupted in C57BL/6J macrophages, this cannot account for the severity of the defect in intracellular growth observed in this strain. Infected macrophages are lost shortly after infection, and at later times a larger fraction of the C57BL/6J macrophages in which L. pneumophila undergoes replication are apoptotic compared to those derived from A/J mice. Finally, a loss of bacterial counts occurs after the first round of growth. Therefore, the resistance mechanism of C57BL/6J macrophages to L. pneumophila infection appears to be multifactorial, and we discuss how early and late responses result in clearing the infection.