Toxoplasma gondii bradyzoites form spontaneously during sporozoite-initiated development?
Toxoplasma gondii bradyzoites form spontaneously during sporozoite-initiated development?
复制标题
DOI：
10.1128/iai.66.10.4838-4844.1998
复制
发表时间：
1998-10-01
影响因子：
3.1
通讯作者：
White, MW
中科院分区：
文献类型：
--
作者：
Jerome, ME;Radke, JR;White, MW
从感染弓形虫子孢子的宿主细胞中出现的速殖子（VEG株）增殖相对较快，每6 h其数量翻一番，这种生长速率是内在的，因为入侵的宿主细胞数量和宿主细胞类型似乎都不影响速殖子的复制。速殖子的快速增长并不持久，在类似于20次分裂之后，种群均匀地转向较慢的增长。寄生虫孢子感染后10天增加一倍，每15小时，不像紧急速殖子，他们在几个月的连续细胞培养中以这种较慢的速度增长。速殖子生长速率的自发变化先于缓殖子特异性标志物BAG 1的表达。在生长转变的24小时内，2%的群体表达BAG 1，并且在子孢子感染后15天，50%的寄生虫对该标志物呈阳性。自发BAG 1的表达，没有观察到在子孢子或速殖子在快速生长（通过第6天后接种子孢子），虽然这些速殖子可以诱导表达BAG 1更早地通过培养子孢子感染的细胞在pH 8.3。然而，碱处理也减少了紧急速殖子的复制率增长转移的寄生虫，支持减少寄生虫生长和缓殖子分化之间的联系。向缓慢生长的转变与小鼠的毒力密切相关，因为最初快速生长的速殖子是无毒的（100%致死剂量，>10（4）个寄生虫），而不能生长转变的突变VEG菌株（MS-J）在接种10个寄生虫的小鼠中引起100%死亡率，从γ干扰素敲除小鼠中回收的寄生虫接种了紧急速殖子，以缓慢的速度生长并表达BAG 1，证实了复制转换发生在动物中，并且在没有保护性免疫应答的情况下。
Tachyzoites (VEG strain) that emerge from host cells infected with Toxoplasma 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 similar to 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 express BAG1 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, >10(4) 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.