Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes
Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes
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DOI：
10.1189/jlb.0103015
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发表时间：
2003-12-01
影响因子：
5.5
通讯作者：
Dornand, J
中科院分区：
文献类型：
--
作者：
Rittig, MG;Kaufmann, A;Dornand, J
细胞内病原体布鲁氏菌对人类的毒力主要与其脂多糖（LPS）表型相关，光滑的LPS表型通常是有毒的，而粗糙的则不是。这种联系的原因尚不十分清楚。我们现在证明，通过流式细胞术，电子显微镜和ELISA，人外周血单核细胞相互作用的定量和定性的光滑和粗糙的布鲁氏菌生物体在体外不同。我们证实，相当高的数量的粗糙比光滑布鲁氏菌附着并进入单核细胞在nonopsonic条件下，但只有光滑布鲁氏菌复制宿主细胞。我们第一次发现粗糙的布鲁氏菌比光滑的布鲁氏菌诱导更多的CXC（GRO-α，IL-8）和CC（MIP-1 α，MIP-1 β，MCP-1，RANTES）趋化因子，以及前体（IL-6，TNF-α）和抗炎（IL-10）细胞因子释放的挑战单核细胞。在摄取后，含有粗糙布鲁氏菌的吞噬体发展选择性融合能力，形成宽敞的公共隔间，而含有光滑布鲁氏菌的吞噬体是非融合的。总的来说，我们的数据表明，粗糙布鲁氏菌吸引和感染单核细胞更有效地比光滑布鲁氏菌，但只有光滑LPS表型建立一个特定的宿主细胞室允许成功的寄生。这些新发现将布鲁氏菌的LPS表型与其在感染宿主细胞水平上对人类的毒力联系起来。这是由于LPS分子的直接作用还是由于上游细菌机制仍有待确定。J. Leukoc. 74：1045-1055; 2003.
Virulence of the intracellular pathogen Brucella for humans is mainly associated with its lipopolysaccharide (LPS) phenotype, with smooth LPS phenotypes generally being virulent and rough ones not. The reason for this association is not quite understood. We now demonstrate by flow cytometry, electron microscopy, and ELISA that human peripheral blood monocytes interact both quantitatively and qualitatively different with smooth and rough Brucella organisms in vitro. We confirm that considerably higher numbers of rough than smooth brucellae attach to and enter the monocytes in nonopsonic conditions; but only smooth brucellae replicate in the host cells. We show for the first time that rough brucellae induce higher amounts than smooth brucellae of several CXC (GRO-alpha, IL-8) and CC (MIP-1alpha, MIP-1beta, MCP-1, RANTES) chemokines, as well as pro(IL-6, TNF-alpha) and anti-inflammatory (IL-10) cytokines released by challenged monocytes. Upon uptake, phagosomes containing rough brucellae develop selective fusion competence to form spacious communal compartments, whereas phagosomes containing smooth brucellae are nonfusiogenic. Collectively, our data suggest that rough brucellae attract and infect monocytes more effectively than smooth brucellae, but only smooth LPS phenotypes establish a specific host cell compartment permitting successful parasitism. These novel findings link the LPS phenotype of Brucella and its virulence for humans at the level of the infected host cells. Whether this is due to a direct effect of the LPS molecules or to upstream bacterial mechanisms remains to be established. J. Leukoc. Biol. 74: 1045-1055; 2003.