Kan-Sutton Celestine, Jagannath Chinnaswamy, Hunter Robert L
Department of Pathology and Laboratory Medicine, The University of Texas at Houston Health Science Center, 6431 Fannin Street, Houston, TX 77030, USA.
Microbes Infect. 2009 Jan;11(1):40-8. doi: 10.1016/j.micinf.2008.10.006. Epub 2008 Nov 1.
Trehalose 6,6'-dimycolate (TDM) is the most abundant lipid extracted from Mycobacterium tuberculosis (MTB). TDM promotes MTB survival by decreasing phagosomal acidification and phagolysosomal fusion in macrophages. Delipidation of MTB using petroleum ether removes TDM and decreases MTB survival within host cells. TDM reconstituted onto MTB restores its virulent wild-type characteristics. We investigated the role of TDM in regulating surface marker expression in MTB-infected macrophages. Macrophages were infected with wild-type, delipidated, and TDM-reconstituted MTB for 24h and measured for changes in surface marker expression. TDM on MTB was found to specifically target MHCII, CD1d, CD40, CD80 and CD86. Both wild-type and TDM-reconstituted MTB suppressed or induced no change in expression of these surface markers, whereas delipidated MTB increased expression of the same markers. MTB-infected macrophages were also overlaid with MHCII-restricted T cell hybridomas which recognize Antigen 85B. Macrophages infected by wild-type and TDM-reconstituted MTB did not present antigen as well as delipidated MTB-infected macrophages. The evidence shown furthers supports the notion that TDM present on MTB promotes its survival and persistence in host macrophages.
海藻糖6,6'-二霉菌酸酯（TDM）是从结核分枝杆菌（MTB）中提取的最丰富的脂质。TDM通过降低巨噬细胞中的吞噬体酸化和吞噬溶酶体融合来促进MTB的存活。用石油醚对MTB进行脱脂可去除TDM并降低MTB在宿主细胞内的存活率。重新构建到MTB上的TDM可恢复其有毒的野生型特征。我们研究了TDM在调节MTB感染的巨噬细胞表面标志物表达中的作用。巨噬细胞用野生型、脱脂型和TDM重构型MTB感染24小时，并测量表面标志物表达的变化。发现MTB上的TDM特异性靶向MHCII、CD1d、CD40、CD80和CD86。野生型和TDM重构型MTB均抑制或未诱导这些表面标志物的表达发生变化，而脱脂型MTB则增加了相同标志物的表达。MTB感染的巨噬细胞还用识别抗原85B的MHCII限制性T细胞杂交瘤覆盖。野生型和TDM重构型MTB感染的巨噬细胞与脱脂型MTB感染的巨噬细胞相比，抗原呈递能力较弱。所示证据进一步支持了MTB上存在的TDM促进其在宿主巨噬细胞中存活和持续存在的观点。
