期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 5, 页码 3332-3341出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.146761
关键词
-
资金
- Fondo de Investigaciones Sanitarias [FIS-ISCIII-00/3073, PI01/3128, PI03-1009, PI07-0289, PI04-0324, CA06-0062]
- Ministerio de Ciencia, Investigacion e Innovacion [BIO2002-0628, SAF-2006-08968, SAF2009-08695]
- Deutsche Forschungsgemeinschaft [SA683/6-1]
- Cluster of Excellence Inflammation at Interfaces
- Fundacion Marques de Valdecilla-Instituto de Formacion e Investigacion Marques de Valdecilla [API09-SAF2009-08695]
The innate immune response to Listeria monocytogenes depends on phagosomal bacterial degradation by macrophages. Here, we describe the role of LIMP-2, a lysosomal type III transmembrane glycoprotein and scavenger-like protein, in Listeria phagocytosis. LIMP-2-deficient mice display a macrophage-related defect in Listeria innate immunity. They produce less acute phase pro-inflammatory cytokines/chemokines, MCP-1, TNF-alpha, and IL-6 but normal levels of IL-12, IL-10, and IFN-gamma and a 25-fold increase in susceptibility to Listeria infection. This macrophage defect results in a low listericidal potential, poor response to TNF-alpha activation signals, impaired phago-lysosome transformation into antigen-processing compartments, and uncontrolled LM cytosolic growth that fails to induce normal levels of acute phase pro-inflammatory cytokines. LIMP-2 transfection of CHO cells confirmed that LIMP-2 participates in the degradation of Listeria within phagosomes, controls the late endosomal/lysosomal fusion machinery, and is linked to the activation of Rab5a. Therefore, the role of LIMP-2 appears to be connected to the TNF-alpha-dependent and early activation of Listeria macrophages through internal signals linking the regulation of late trafficking events with the onset of the innate Listeria immune response.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据