Factors Influencing Tissue Cyst Yield in a Murine Model of Chronic Toxoplasmosis.

Factors Influencing Tissue Cyst Yield in a Murine Model of Chronic Toxoplasmosis.
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DOI:
10.1128/iai.00566-22
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发表时间:
2023-07-18
影响因子:
3.1
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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最近对弓形虫组织囊肿及其所容纳的慢殖子的独特生物学的研究进展需要优化从感染小鼠大脑中恢复的组织囊肿。在这里,我们提供了在3年的时间里对CBA/J小鼠II型ME49组织囊肿进行83次组织囊肿纯化的数据。评估了组织培养速殖子和离体组织囊肿感染的影响。显著的死亡率仅限于速殖子感染,雌性小鼠更容易感染。组织囊肿感染与较低的总体症状和死亡率相关,没有性别偏见。总的来说,尽管速殖子引发的感染产生的产量明显高于组织囊肿引发的感染,但宿主性别对组织囊肿的总体产量没有影响。值得注意的是,组织囊肿的连续传代伴随着随后囊肿恢复的减少趋势。组织囊肿收获的时间是缓殖子生理状态的潜在反映,在选定的时间点对随后的囊肿产量没有显著影响。总的来说,这些数据揭示了与组织囊肿产量相关的相当大的异质性,使得设计足够有力的实验至关重要。在药物研究中尤其如此,目前,总体组织囊肿负荷是衡量疗效的主要且通常是唯一的指标,因为本文提供的数据表明,未经治疗的动物制剂之间的囊肿恢复可以反映甚至超过所报道的药物治疗效果。
Recent advances into the unique biology of Toxoplasma tissue cysts and the bradyzoites they house necessitate optimization of tissue cyst recovery from infected mouse brains. Here, we present data from 83 tissue cyst purifications of Type II ME49 tissue cysts in CBA/J mice performed over a period of 3 years. The effects of infection with both tissue culture tachyzoites as well as ex vivo tissue cysts were assessed. Significant mortality was restricted to tachyzoite infections with female mice being more susceptible. Infection with tissue cysts was associated with both lower overall symptomology and mortality, exhibiting no sex bias. Cumulatively, host sex did not impact overall tissue cyst yields, although tachyzoite-initiated infections generated significantly higher yields compared to tissue cyst-initiated infections. Notably, serial passage of tissue cysts was accompanied with a decreasing trend for subsequent cyst recovery. The time of tissue cyst harvest, a potential reflection of bradyzoite physiological state, had no significant impact on subsequent cyst yield at the selected time points. In aggregate, these data reveal the considerable heterogeneity associated with tissue cyst yield, making the design of adequately powered experiments critical. This is particularly the case for drug studies where overall tissue cyst burden is currently the primary and often sole metric of efficacy, as the data presented here demonstrate that cyst recovery between preparations of untreated animals can mirror and even exceed the reported effects of drug treatment.
弓形虫病发育中的药物:进步,挑战和当前状态。
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