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Toxoplasma Gondii Bradyzoites Form Spontaneously during Sporozoite-Initiated Development

机译：弓形虫缓殖子在子孢子引发的发育过程中自发形成。

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Tachyzoites (VEG strain) that emerge from host cells infected withToxoplasma gondii sporozoites proliferate relatively fast and double their number every 6 h. This rate of growth is intrinsic, as neither the number of host cells invaded nor host cell type appears to influence emergent tachyzoite replication. Fast tachyzoite growth was not persistent, and following ～20 divisions, the population uniformly shifted to slower growth. Parasites 10 days post-sporozoite infection doubled only once every 15 h and, unlike emergent tachyzoites, they grew at this slower rate over several months of continuous cell culture. The spontaneous change in tachyzoite growth rate preceded the expression of the bradyzoite-specific marker,BAG1. Within 24 h of the growth shift, 2% of the population expressed BAG1, and by 15 days post-sporozoite infection, 50% of the parasites were positive for this marker. Spontaneous BAG1 expression was not observed in sporozoites or in tachyzoites during fast growth (through day 6 post-sporozoite inoculation), although these tachyzoites could be induced to expressBAG1 earlier by culturing sporozoite-infected cells at pH 8.3. However, alkaline treatment also reduced the replication of emergent tachyzoites to the rate of growth-shifted parasites, supporting a link between reduced parasite growth and bradyzoite differentiation. The shift to slower growth was closely correlated with virulence in mice, as the initially fast-growing emergent tachyzoites were avirulent (100% lethal dose, >104 parasites), while a mutant VEG strain (MS-J) that is unable to growth shift caused 100% mortality in mice inoculated with 10 parasites. Parasites recovered from gamma interferon knockout mice inoculated with emergent tachyzoites grew at a slow rate and expressed BAG1, confirming that the replication switch occurs in animals and in the absence of a protective immune response.
机译：刚地弓形虫子孢子感染的宿主细胞中出现的速殖子（VEG株）增殖速度相对较快，每6小时就会增加一倍。这种生长速率是固有的，因为入侵的宿主细胞数量和宿主细胞类型均不会影响新生速殖子的复制。速殖子的快速生长不是持久的，经过20个分裂之后，种群均匀地转移到了较慢的生长上。子孢子感染后10天的寄生虫每15小时仅翻一倍，并且与新生的速殖子不同，它们在连续细胞培养的几个月中以这种较慢的速度生长。速殖子生长速率的自发变化先于缓殖子特异性标记 BAG1 的表达。在生长变化的24小时内，有2％的人群表达了 BAG1 ，到子孢子虫感染后15天，有50％的寄生虫对该标志物呈阳性。在快速生长期间（直至子孢子接种后第6天），子孢子或速殖子中均未观察到自发的 BAG1 表达，尽管通过培养这些速殖子可以更早地表达 BAG1 。 pH 8.3的子孢子感染的细胞。但是，碱处理也将出现的速殖子的复制减少到生长移位的寄生虫的速率，从而支持了寄生虫生长减少和缓殖子分化之间的联系。生长缓慢的转变与小鼠的毒力密切相关，因为最初快速生长的速生速殖子是无毒的（100％致死剂量，> 10 4 寄生虫），而突变的VEG株（MS- J）无法生长转移导致接种10种寄生虫的小鼠死亡100％。从接种了速殖子的伽马干扰素敲除小鼠中回收的寄生虫以缓慢的速度生长并表达 BAG1 ，这证实了复制开关在动物体内发生并且没有保护性免疫应答。

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