Role of fusogenic non-PC liposomes in elicitation of protective immune response against experimental murine salmonellosis
Role of fusogenic non-PC liposomes in elicitation of protective immune response against experimental murine salmonellosis
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DOI：
10.1016/j.biochi.2006.04.017
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发表时间：
2006-10-01
期刊：
影响因子：
3.9
通讯作者：
Owais, M.
中科院分区：
文献类型：
--
作者：
Ahmad, N.;Deeba, F.;Owais, M.
先前我们已经证明，由大肠杆菌脂质组成的新型融合性脂质体（escheriosomes）具有与靶细胞的质膜融合的强烈倾向，从而将被捕获的内容物输送到细胞质溶胶中。被包裹的抗原在靶细胞的细胞质中传递，随后随着MHC I类途径进行加工和递呈，最终引发抗原特异性细胞毒性T细胞。本研究结果表明，用包被鼠伤寒沙门菌（S. typhimurium）胞浆抗原免疫BALB/c小鼠可增强抗原特异性细胞毒性T细胞淋巴细胞和IgG应答。相比之下，自由或传统脂质体（PC脂质体）包封抗原在免疫动物中不能诱导CD8+ ctl。此外，用escheroome包封抗原免疫可显著增强实验动物体内ifn - γ和IgG2a的释放。有趣的是，escherosomes包封抗原免疫也导致抗原呈递细胞（APCs）表面CD80和CD86的上调。最后，本研究的结果表明，用大肠杆菌包封抗原免疫动物可以保护它们免受毒力强的鼠伤寒沙门氏菌感染。这是显而易见的，增加了存活率，减少了免疫动物重要器官的细菌负担。本研究的数据表明，大肠杆菌小体可以作为细胞内递送抗原的有效载体，因此有望开发基于脂质体的疫苗，以对抗沙门氏菌和其他细胞内病原体。(c) 2006 Elsevier Masson SAS。版权所有。
Earlier we have demonstrated that novel fusogenic liposomes made up of lipid from Escherichia coli (escheriosomes) have strong tendency to fuse with the plasma membrane of target cells and thereby delivering the entrapped contents into their cytosol. The delivery of entrapped antigen in cytosol of the target cells ensues its processing and presentation along with MHC class I pathway that eventually elicit antigen specific cytotoxic T cells. The result of the present study revealed that immunization of BALB/c mice with escheriosome-encapsulated Salmonella typhimurium (S. typhimurium) cytosolic antigens resulted in the augmentation of antigen specific cytotoxic T cell lymphocyte as well as IgG responses. In contrast, free or conventional liposome (PC liposome) encapsulated antigen failed to induce CD8+ CTLs in the immunized animals. Further, immunization with escheriosome-encapsulated antigen resulted in significant enhancement in the release of IFN-gamma and IgG2a in the experimental animals. Interestingly, the immunization with escheriosome-encapsulated antigen resulted in upregulation of CD80 and CD86 on the surface of antigen presenting cells (APCs) as well. Finally, the results of the present study reveal that immunization of animals with escheriosomes encapsulated antigen protected them against virulent S. typhimurium infection. This was evident by increased survival, and reduced bacterial burden in vital organs of the immunized animals. The data of the present study suggest that escheriosomes can emerge as an effective vehicle for intracellular delivery of antigen and thus hold promise in development of liposome based vaccine against Salmonella and other intracellular pathogens. (c) 2006 Elsevier Masson SAS. All rights reserved.