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Trypanosoma cruzi amastigotes that persist in the colon during chronic stage murine infections have a reduced replication rate
Open Biology ( IF 5.8 ) Pub Date : 2020-12-16 , DOI: 10.1098/rsob.200261
Alexander I Ward 1 , Francisco Olmo 1 , Richard L Atherton 1 , Martin C Taylor 1 , John M Kelly 1
Affiliation  

Chronic Trypanosoma cruzi infections are typically lifelong, with small numbers of parasites surviving in restricted tissue sites, which include the gastrointestinal tract. There is considerable debate about the replicative status of these persistent parasites and whether there is a role for dormancy in long-term infection. Here, we investigated T. cruzi proliferation in the colon of chronically infected mice using 5-ethynyl-2′deoxyuridine incorporation into DNA to provide ‘snapshots’ of parasite replication status. Highly sensitive imaging of the extremely rare infection foci, at single-cell resolution, revealed that parasites are three times more likely to be in S-phase during the acute stage than during the chronic stage. By implication, chronic infections of the colon are associated with a reduced rate of parasite replication. Despite this, very few host cells survived infection for more than 14 days, suggesting that T. cruzi persistence continues to involve regular cycles of replication, host cell lysis and re-infection. We could find no evidence for wide-spread dormancy in parasites that persist in this tissue reservoir.



中文翻译:

慢性期鼠感染期间在结肠中持续存在的克氏锥虫无鞭毛体复制率降低

慢性克氏锥虫感染通常是终生的,少数寄生虫在包括胃肠道在内的受限组织部位存活。关于这些持久性寄生虫的复制状态以及休眠是否在长期感染中起作用存在相当大的争论。在这里,我们调查了 T. cruzi使用 5-乙炔基-2'脱氧尿苷掺入 DNA 以提供寄生虫复制状态的“快照”在慢性感染小鼠的结肠中增殖。以单细胞分辨率对极其罕见的感染病灶进行高度敏感的成像显示,寄生虫在急性期处于 S 期的可能性是慢性期的三倍。暗示,结肠的慢性感染与寄生虫复制率降低有关。尽管如此,很少有宿主细胞在感染后存活超过 14 天,这表明T. cruzi持续存在继续涉及复制、宿主细胞裂解和再感染的定期循环。我们找不到任何证据表明存在于该组织储库中的寄生虫广泛休眠。

更新日期:2020-12-16
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