Replication of Yersinia pestis in interferon γ-activated macrophages requires ripA, a gene encoded in the pigmentation locus
Replication of Yersinia pestis in interferon γ-activated macrophages requires ripA, a gene encoded in the pigmentation locus
复制标题
DOI：
10.1073/pnas.0502849102
复制
发表时间：
2005-09-06
影响因子：
11.1
通讯作者：
Bliska, JB
中科院分区：
文献类型：
--
作者：
Pujol, C;Grabenstein, JP;Bliska, JB
鼠疫耶尔森菌是一种兼性胞内细菌病原体，可在巨噬细胞中复制。关于Y.鼠疫菌在巨噬细胞中复制，巨噬细胞防御机制对限制鼠疫菌的细胞内存活很重要。鼠疫还没有被定性。在这项工作中，我们研究了Y。鼠疫杆菌在用IFN-γ激活的原代鼠巨噬细胞中复制。Y.鼠疫杆菌能够在感染后用IFN-γ活化的巨噬细胞中复制（活化后）。被称为色素沉着（pgm）基因座的染色体DNA区域是激活后巨噬细胞复制所必需的，这种复制与一氧化氮（NO）水平降低有关，但与诱导型NO合酶（iNOS）表达降低无关。Y.鼠疫Δ pgm在用IFN-γ后活化的NOS-/-巨噬细胞中复制，表明Δ pgm Y.鼠疫是NO依赖性的。pgm中的一个特定的遗传位点，与沙门氏菌中的致病岛相似，被证明是Y。鼠疫和限制NO水平在后激活的巨噬细胞。这些数据表明，细胞内Y。鼠疫菌可以逃避暴露于IFN-γ的巨噬细胞的杀伤，并鉴定出这种活性所需的pgm基因座中编码的潜在毒力基因。
Yersinia pestis is a facultative intracellular bacterial pathogen that can replicate in macrophages. Little is known about the mechanism by which Y. pestis replicates in macrophages, and macrophage defense mechanisms important for limiting intracellular survival of Y. pestis have not been characterized. In this work, we investigated the ability of Y. pestis to replicate in primary murine macrophages that were activated with IFN-gamma. Y. pestis was able to replicate in macrophages that were activated with IFN-gamma after infection (postactivated). A region of chromosomal DNA known as the pigmentation (pgm) locus was required for replication in postactivated macrophages, and this replication was associated with reduced nitric oxide (NO) levels but not with reduced inducible NO synthase (iNOS) expression. Y. pestis Delta pgm replicated in NOS-/- macrophages that were postactivated with IFN-gamma, suggesting that killing of Delta pgm Y. pestis is NO-dependent. A specific genetic locus within pgm, which shares similarity to a pathogenicity island in Salmonella, was shown to be required for replication of Y. pestis and restriction of NO levels in postactivated macrophages. These data demonstrate that intracellular Y. pestis can evade killing by macrophages that are exposed to IFN-gamma and identify a potential virulence gene encoded in the pgm locus that is required for this activity.