Francisella tularensis Confronts the Complement System
Francisella tularensis Confronts the Complement System
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DOI：
10.3389/fcimb.2017.00523
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发表时间：
2017-12-19
影响因子：
5.7
通讯作者：
Parmely, Michael J.
中科院分区：
文献类型：
--
作者：
Brock, Susan R.;Parmely, Michael J.
土拉弗朗西斯菌已经开发出许多有效的逃避策略来对抗宿主的免疫防御，其中最重要的是它能够与补体系统相互作用以发挥其自身的优势。将细菌暴露于新鲜人血清后，补体被激活，并且可以发现 C3b 和 iC3b 共价附着在细菌表面。然而，土拉菌细胞壁的脂多糖和荚膜可防止补体介导的裂解，并赋予细菌血清抗性。 C3 对 tularensis 的调理作用大大增加了人类中性粒细胞、树突状细胞和巨噬细胞对其的摄取。人类巨噬细胞通过异常的循环形态进行摄取。补体受体 3 被认为在人类巨噬细胞的调理吞噬作用中发挥重要作用，并且通过该受体的信号传导可以拮抗 Toll 样受体 2 引发的巨噬细胞激活。补体 C3 还决定受感染的人类巨噬细胞以及其他细胞类型的存活。 F. tularensis 亚种的 C3 调理作用。 tularensis 菌株 SCHU S4 会导致受感染的人类巨噬细胞死亡大大增加，这需要的不仅仅是补体受体的参与，而且与病原体的细胞内复制无关。鉴于其进入宿主细胞的细胞质，F tularensis 具有许多其他补体介导的相互作用的潜力。对摄取 C3 调理腺病毒的研究表明，存在 C3 传感系统，该系统启动细胞对入侵微生物上存在的胞质 C3b 做出反应。在这里，我们提出 C3 肽在 F tularensis 吞噬体逃逸后进入人类巨噬细胞的胞质溶胶，并被认为是发出宿主细胞死亡信号的入侵分子模式。随着细胞内 C3 新作用的发现，人们可能会更好地了解土拉菌病的发病机制。
Francisella tularensis has developed a number of effective evasion strategies to counteract host immune defenses, not the least of which is its ability to interact with the complement system to its own advantage. Following exposure of the bacterium to fresh human serum, complement is activated and C3b and iC3b can be found covalently attached to the bacterial surface. However, the lipopolysaccharide and capsule of the F tularensis cell wall prevent complement-mediated lysis and endow the bacterium with serum resistance. Opsonization of F. tularensis with C3 greatly increases its uptake by human neutrophils, dendritic cells and macrophages. Uptake occurs by an unusual looping morphology in human macrophages. Complement receptor 3 is thought to play an important role in opsonophagocytosis by human macrophages, and signaling through this receptor can antagonize Toll-like receptor 2-initiated macrophage activation. Complement C3 also determines the survival of infected human macrophages and perhaps other cell types. C3-opsonization of F. tularensis subsp. tularensis strain SCHU S4 results in greatly increased death of infected human macrophages, which requires more than complement receptor engagement and is independent of the intracellular replication by the pathogen. Given its entry into the cytosol of host cells, F tularensis has the potential for a number of other complement-mediated interactions. Studies on the uptake C3-opsonized adenovirus have suggested the existence of a C3 sensing system that initiates cellular responses to cytosolic C3b present on invading microbes. Here we propose that C3 peptides enter the cytosol of human macrophages following phagosome escape of F tularensis and are recognized as intruding molecular patterns that signal host cell death. With the discovery of new roles for intracellular C3, a better understanding of tularemia pathogenesis is likely to emerge.