A quorum sensing-independent path to stumpy development in Trypanosoma brucei

For persistent infections of the mammalian host, African trypanosomes limit their population size by quorum sensing of the parasite-excreted stumpy induction factor (SIF), which induces development to the tsetse-infective stumpy stage. We found that besides this cell density-dependent mechanism, there exists a second path to the stumpy stage that is linked to antigenic variation, the main instrument of parasite virulence. The expression of a second variant surface glycoprotein (VSG) leads to transcriptional attenuation of the VSG expression site (ES) and immediate development to tsetse fly infective stumpy parasites. This path is independent of SIF and solely controlled by the transcriptional status of the ES. In pleomorphic trypanosomes varying degrees of ES-attenuation result in phenotypic plasticity. While full ES-attenuation causes irreversible stumpy development, milder attenuation may open a time window for rescuing an unsuccessful antigenic switch, a scenario that so far has not been considered as important for parasite survival.

针对哺乳宿主的持续性感染，非洲锥虫可通过对寄生虫分泌的矮化诱导因子（stumpy induction factor, SIF）进行群体感应，以此限制种群规模，进而诱导其发育为可感染采采蝇的矮虫阶段。本研究发现，除这种依赖细胞密度的调控机制外，还存在第二条通往矮虫阶段的通路，该通路与寄生虫毒力的核心工具——抗原变异密切相关。第二种变异表面糖蛋白（variant surface glycoprotein, VSG）的表达，会引发VSG表达位点（VSG expression site, ES）的转录衰减，并直接促使锥虫发育为可感染采采蝇的矮虫阶段。该通路不依赖SIF，仅由ES的转录状态调控。在多形性锥虫中，不同程度的ES衰减会带来表型可塑性：完全的ES衰减会导致不可逆的矮虫发育，而轻度衰减则可能为挽救失败的抗原变异提供时间窗口——这一情境此前未被认为对寄生虫存活具有重要意义。