Cell density triggers slender to stumpy differentiation of Trypanosoma brucei bloodstream forms in culture
Cell density triggers slender to stumpy differentiation of Trypanosoma brucei bloodstream forms in culture
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DOI：
10.1016/s0166-6851(97)00160-6
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发表时间：
1997-12-01
影响因子：
1.5
通讯作者：
Boshart, M
中科院分区：
文献类型：
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作者：
Reuner, B;Vassella, E;Boshart, M
除了抗体反应之外且独立于抗体反应，布氏锥虫从复制细长形式分化为不分裂的粗短血流形式，限制了哺乳动物宿主中的寄生虫种群大小。使用布氏锥虫多形性菌株的培养系统，我们发现细长形式在体外非常有效地分化为短粗形式，并且分化的诱导与细胞密度相关。使用一系列标记物比较宿主和培养物中的分化，包括细胞形态和体积、细胞周期位置、分化动力学、NADH脱氢酶（心肌黄酶）的表达、几种差异调节转录物的表达以及顺乌头酸诱导后向复制原循环形式转化的动力学。根据所有可用的标准，培养物的分化反映了哺乳动物宿主的自然过程。时程实验揭示了血流形式的细胞周期停滞、粗短分化标记物的出现以及血流形式群体响应顺乌头酸而启动向前循环形式转变的能力之间存在非常紧密的时间相关性。我们的结果表明，血流形态分化的诱导可以独立于宿主衍生的线索而发生。我们提出了一种密度传感机制，可诱导分化为非分裂残端阶段，从而使寄生虫种群能够自动调节其增殖。 (C) 1997 Elsevier Science B.V.
Differentiation from replicating slender forms to non-dividing stumpy bloodstream forms of T. brucei limits the parasite population size in the mammalian host in addition to and independently of the antibody response. Using a culture system for pleomorphic strains of T. brucei we show that slender forms very efficiently differentiate to stumpy forms in vitro and that the induction of differentiation is correlated to cell density. Differentiation in the host and in culture were compared using a battery of markers including cell morphology and volume, cell cycle position, the kinetics of the differentiation, expression of NADH dehydrogenase (diaphorase), expression of several differentially regulated transcripts and the kinetics of transformation to replicating procyclic forms after induction with cis-aconitate. By all available criteria, differentiation in culture reflects the natural process in the mammalian host. Time course experiments reveal a very tight temporal correlation between cell cycle arrest of bloodstream forms, appearance of a stumpy differentiation marker and the competence of a bloodstream form population to initiate transformation to procyclic forms in response to cis-aconitate. Our results show that induction of bloodstream form differentiation can occur independently of host-derived cues. We suggest a density sensing mechanism which induces differentiation to the non-dividing stumpy stage and thereby enables the parasite population to autoregulate its proliferation. (C) 1997 Elsevier Science B.V.