Evasion of Macrophage Lysosomes by L pneumophilia

先天性和获得性免疫反应是由巨噬细胞吞噬启动的，巨噬细胞是一种复杂的细胞 目前还没有完全了解的途径。为了研究吞噬小体成熟是如何控制的，细菌 嗜肺军团菌可作为巨噬细胞功能的遗传探针。上一首 研究支持嗜肺性乳杆菌通过表达吞噬小体-溶酶体融合来阻止其融合的假说 至少有两项活动是受发育调节的。 吞噬小体成熟抑制物何时、如何和在何处表达的知识 嗜肺性乳杆菌将用于鉴定相应的分子。细菌表面的因子 阻断吞噬小体-溶酶体融合将通过分离和表征突变来寻求遗传学上的 影响DOTA突变体在巨噬细胞中的持久性、凝集素结合或碳氢化合物结合，以及 通过比较强毒和无毒菌株表面蛋白质和碳水化合物的谱来进行生化分析 菌株。指数期后细菌表达的阻止与溶酶体融合的因子也将是 通过其构成表达将调节突变体从溶酶体杀死中拯救出来的基因来鉴定。 通过了解嗜肺乳杆菌如何逃避巨噬细胞的清除，人们可以推断这些 吞噬细胞例行公事地吞噬、消化和展示外来物质，然后聘请专家来消除潜在的 威胁。由于巨噬细胞在体液免疫和细胞免疫中都是中心效应细胞，因此 对它们的膜交通的分子描述可能会提供无数的机会来改进 提供预防和治疗各种人类疾病的治疗药物。

Innate and adaptive immune responses are initiated by macrophage phagocytosis, a complex cellular pathway that is not yet fully understood. To investigate how phagosome maturation is governed, the bacterial pathogen Legionella pneumophila can be exploited as a genetic probe of macrophage function. Previous studies support the hypothesis that L. pneumophila blocks phagosome-lysosome fusion by expressing on its surface at least two activities that are developmentally regulated. Knowledge of when, how and where inhibitors of phagosome maturation are expressed by L. pneumophila will be applied to identify the corresponding molecules. Factors on the bacterial surface that block phagosome-lysosome fusion will be sought genetically by isolating and characterizing mutations that affect either persistence of dotA mutants in macrophages, lectin binding, or hydrocarbon binding, and biochemically by comparing the profiles of surface proteins and carbohydrates of virulent and avirulent strains. Factors expressed by post-exponential phase bacteria to block fusion with lysosomes will also be identified by loci whose constituitive expression rescues a regulatory mutant from lysosomal killing. By understanding how L. pneumophila evades clearance by macrophages, one can deduce how these phagocytes routinely engulf, digest, and display foreign material, then recruit specialists to eliminate potential threats. Because macrophages are central effector cells in both humoral and cell-mediated immunity, a molecular description of their membrane traffic is likely to provide a myriad of opportunities for improving delivery of therapeutics to prevent and treat a variety of human diseases.