Fate of a Burkholderia pseudomallei mouse macrophage cell line lipopolysaccharide mutant in the RAW 264.7:: Possible role for the o-antigenic polysaccharide moiety of lipopolysaccharide in internalization and intracellular survival
Fate of a Burkholderia pseudomallei mouse macrophage cell line lipopolysaccharide mutant in the RAW 264.7:: Possible role for the o-antigenic polysaccharide moiety of lipopolysaccharide in internalization and intracellular survival
复制标题
DOI：
10.1128/iai.00285-07
复制
发表时间：
2007-09-01
影响因子：
3.1
通讯作者：
Utaisincharoen, P.
中科院分区：
文献类型：
--
作者：
Arjcharoen, S.;Wikraiphat, C.;Utaisincharoen, P.
类鼻疽伯克霍尔德菌是一种兼性细胞内革兰氏阴性细菌，可以在巨噬细胞内存活和繁殖。B.假鼻疽逃避巨噬细胞杀伤的方法是干扰诱导型一氧化氮合酶（iNOS）的表达。然而，调节巨噬细胞抗菌活性的细菌组分尚未完全阐明。在本研究中，我们证明了B。类鼻疽菌菌株SRM 117，一种缺乏O-抗原多糖部分的脂多糖（LPS）突变体，在感染的早期阶段比亲本野生型菌株（1026 b）更容易被巨噬细胞杀死。与野生型不同，LPS突变体可以容易地刺激Y 701-STAT-1磷酸化（pY 701-STAT-1）和干扰素调节因子1（IRF-1）的表达，这两者都是iNOS的必需转录因子。抗β干扰素中和抗体能抑制Y 701-STAT-1的磷酸化及IRF-1和iNOS的表达，所有这些都导致细胞内复制速率的增加。这些数据表明，B的O-抗原多糖部分。类鼻疽调节宿主细胞应答，宿主细胞应答又控制B的细胞内命运。巨噬细胞内的假鼻疽
Burkholderia pseudomallei is a facultative intracellular gram-negative bacterium that can survive and multiply inside macrophages. One of the mechanisms by which B. pseudomallei escapes macrophage killing is by interfering with the expression of inducible nitric oxide synthase (iNOS). However, the bacterial components that modulate antimicrobial activity of the macrophage have not been fully elucidated. In the present study, we demonstrated that B. pseudomallei strain SRM117, a lipopolysaccharide (LPS) mutant that lacks the O-antigenic polysaccharide moiety, was more susceptible to macrophage killing during the early phase of infection than the parental wild-type strain (1026b). Unlike the wild type, the LPS mutant could readily stimulate Y701-STAT-1 phosphorylation (pY701-STAT-1) and interferon-regulatory factor 1 (IRF-1) expression, both of which are essential transcription factors of iNOS. Neutralizing antibody against beta interferon was able to inhibit the phosphorylation of Y701-STAT-1 and the expression of IRF-1 and iNOS, all of which resulted in an increased rate of intracellular replication. These data suggest that the O-antigenic polysaccharide moiety of B. pseudomallei modulates the host cell response, which in turn controls the intracellular fate of B. pseudomallei inside macrophages.