Hampering-surface presentation of immunogenic peptides by class I/II MHCs is a key strategy opted by several intracellular protozoan pathogens including Leishmania to escape CD8/CD4 mediated host-protective T-cell response. Although Leishmania parasites (LP) primarily hijack/inhibit host lysosomal/proteasomal pathways to hamper antigen-processing/presentation machinery, recent pieces of evidence have linked host-membrane fluidity as a major cause of defective antigen presentation in leishmaniasis. Increased membrane fluidity severely compromised peptide-MHC stability in the lipid raft regions, thereby abrogating T-cell mediated-signalling in the infected host. LP primarily achieves this by quenching host cholesterol, which acts as cementing material in maintaining the membrane fluidity. In this review, we have particularly focused on several strategies opted by LP to hijack-host cholesterol resulting in lipid droplets accumulation around leishmania-containing parasitophorous vacuole favouring intracellular survival of LP. In fact, LP infection can result in altered cholesterol and lipid metabolism in the infected host, thereby favouring the establishment and progression of the infection. From our analysis of two genome-wide transcriptomics data sets of LP infected host, we propose a possible molecular network that connects these interrelated events of altered lipid metabolism with eventual compromised antigen presentation, still existing as a gap in our current understanding of Leishmania infection.

中文翻译：

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将膜流动性与利什曼病中抗原呈递缺陷联系起来

I/II 类 MHC 阻碍免疫原性肽的表面呈递是包括利什曼原虫在内的几种细胞内原生动物病原体选择的关键策略，以逃避 CD8/CD4 介导的宿主保护性 T 细胞反应。虽然利什曼原虫寄生虫 (LP) 主要劫持/抑制宿主溶酶体/蛋白酶体途径以阻碍抗原加工/呈递机制，最近的证据表明宿主膜流动性是利什曼病抗原呈递缺陷的主要原因。增加的膜流动性严重损害了脂筏区域中肽-MHC 的稳定性，从而消除了受感染宿主中 T 细胞介导的信号传导。LP 主要通过淬灭宿主胆固醇来实现这一点，宿主胆固醇作为保持膜流动性的胶结材料。在这篇综述中，我们特别关注 LP 选择的几种策略来劫持宿主胆固醇，导致利什曼原虫周围的脂滴积聚-含寄生液泡有利于LP的细胞内存活。事实上，LP 感染可导致受感染宿主的胆固醇和脂质代谢发生改变，从而有利于感染的建立和发展。根据我们对 LP 感染宿主的两个全基因组转录组学数据集的分析，我们提出了一个可能的分子网络，该网络将脂质代谢改变的这些相关事件与最终受损的抗原呈递联系起来，这仍然是我们目前对利什曼原虫感染的理解中的一个空白。