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Plasma Membrane Expression of Heat Shock Protein 60 In Vivo in Response to Infection

机译：感染后体内热休克蛋白60的质膜表达

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Heat shock protein 60 (hsp60) is constitutively expressed in the mitochondria of eukaryotic cells. However, it has been identified in other subcellular compartments in several disease states and in transformed cells, and it is an immunogenic molecule in various infectious and autoimmune diseases. To better understand the factors that influence expression of hsp60 in normal cells in vivo, we analyzed its cellular and subcellular distribution in mice infected with the intracellular bacterium Listeria monocytogenes. Western blotting of subcellular fractionated spleen cells showed that although endogenous hsp60 was restricted to the mitochondria in noninfected animals, it was associated with the plasma membrane as a result of infection. The low levels of plasma membrane-associated hsp60 seen in the livers in noninfected animals subsequently increased during infection. Plasma membrane hsp60 expression did not correlate with bacterial growth, being most evident during or after bacterial clearance and persisting at 3 weeks postinfection. Using flow cytometry, we determined that Mac-1+, T-cell receptor γδ+, and B220+ cells represented the major Hsp60+ populations in spleens of infected mice. By contrast, B220+ cells were the predominant hsp60+ population in livers of infected mice. Of the immune cells analyzed, the kinetic profile of the γδ T-cell response most closely matched that of hsp60 expression in both the spleen and liver. Collectively, these findings show that during infection hsp60 can be localized to the plasma membrane of viable cells, particularly antigen-presenting cells, providing a means by which hsp60-reactive lymphocytes seen in various infectious disease and autoimmune disorders may be generated and maintained.
机译：热休克蛋白60（hsp60）在真核细胞的线粒体中组成性表达。但是，已经在几种疾病状态的其他亚细胞区室和转化细胞中鉴定出了它，并且它是各种传染性和自身免疫性疾病中的一种免疫原性分子。为了更好地了解影响hsp60在体内正常细胞中表达的因素，我们分析了hsp60在感染细胞内单核细胞增生李斯特菌的小鼠中的细胞和亚细胞分布。亚细胞分离的脾细胞的蛋白质印迹显示，尽管内源性hsp60在非感染动物中仅局限于线粒体，但由于感染而与质膜有关。在未感染动物的肝脏中发现的低水平的质膜相关hsp60随后在感染期间增加。质膜hsp60表达与细菌生长无关，在细菌清除期间或之后最为明显，并在感染后3周持续存在。使用流式细胞仪，我们确定Mac-1 + ，T细胞受体γδ + 和B220 + 细胞代表主要的Hsp60 + 种群。相比之下，B220 + 细胞是感染小鼠肝脏中主要的hsp60 + 种群。在所分析的免疫细胞中，γδT细胞反应的动力学特征与脾脏和肝脏中hsp60表达的动力学特征最接近。总的来说，这些发现表明，在感染期间hsp60可以定位在活细胞，特别是抗原呈递细胞的质膜上，提供了一种可以产生和维持在各种感染性疾病和自身免疫性疾病中见到的hsp60反应性淋巴细胞的手段。

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