Inefficient complement system clearance of Trypanosoma cruzi metacyclic trypomastigotes enables resistant strains to invade eukaryotic cells.

Inefficient complement system clearance of Trypanosoma cruzi metacyclic trypomastigotes enables resistant strains to invade eukaryotic cells.
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DOI:
10.1371/journal.pone.0009721
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发表时间:
2010-03-16
期刊:
影响因子:
3.7
通讯作者:
Ramirez MI
Ramirez MI
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cestari I;Ramirez MI

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补体系统是脊椎动物天然免疫系统抵抗病原体感染的主要武器。对于原生动物克氏锥虫(Trypanosoma cruzi),恰加斯病的病原体,破坏补体系统并侵入宿主细胞是成功感染的关键。然而,很少有人关注补体系统是否能有效地控制T。克氏感染为了解决这个问题,我们决定分析:1)哪些补体途径被T激活。cruzi的研究; 2)这些菌株在接近生理条件下抵抗补体介导的杀伤的能力;真核细胞的Cruzi侵袭。补体激活分子C1 q、C3、甘露聚糖结合凝集素和纤维胶凝蛋白与所有分析的菌株结合; Cruzi主要激活非免疫人血清中的凝集素和替代补体途径。引人注目的是,我们检测到一些T。Cruzi菌株对非免疫血清中补体介导的杀伤高度敏感,而其它菌株具有抗性。此外,非免疫血清可降低寄生虫对真核细胞的侵袭率。总之,这些结果表明,补体系统识别T。克氏亚环锥鞭毛体,导致敏感菌株死亡。因此,补体系统作为一种生理屏障,耐药菌株必须逃避成功的宿主感染。
The complement system is the main arm of the vertebrate innate immune system against pathogen infection. For the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, subverting the complement system and invading the host cells is crucial to succeed in infection. However, little attention has focused on whether the complement system can effectively control T. cruzi infection. To address this question, we decided to analyse: 1) which complement pathways are activated by T. cruzi using strains isolated from different hosts, 2) the capacity of these strains to resist the complement-mediated killing at nearly physiological conditions, and 3) whether the complement system could limit or control T. cruzi invasion of eukaryotic cells. The complement activating molecules C1q, C3, mannan-binding lectin and ficolins bound to all strains analysed; however, C3b and C4b deposition assays revealed that T. cruzi activates mainly the lectin and alternative complement pathways in non-immune human serum. Strikingly, we detected that metacyclic trypomastigotes of some T. cruzi strains were highly susceptible to complement-mediated killing in non-immune serum, while other strains were resistant. Furthermore, the rate of parasite invasion in eukaryotic cells was decreased by non-immune serum. Altogether, these results establish that the complement system recognizes T. cruzi metacyclic trypomastigotes, resulting in killing of susceptible strains. The complement system, therefore, acts as a physiological barrier which resistant strains have to evade for successful host infection.
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