APOL1 expression is induced by Trypanosoma brucei gambiense infection but is not associated with differential susceptibility to sleeping sickness
APOL1 expression is induced by Trypanosoma brucei gambiense infection but is not associated with differential susceptibility to sleeping sickness
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DOI：
10.1016/j.meegid.2012.05.010
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发表时间：
2012-10-01
影响因子：
3.2
通讯作者：
Bucheton, Bruno
中科院分区：
文献类型：
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作者：
Ilboudo, Hamidou;Berthier, David;Bucheton, Bruno
大多数非洲锥虫物种对人血清中存在的锥虫溶解因子（TLF）敏感。锥虫溶解被证明与载脂蛋白L-1（APOL 1）有关。布氏锥虫（Trypanosomabrucei，T. B.）冈比亚锥虫和布氏锥虫罗得西亚锥虫（两种人类感染性锥虫物种）都发展了对APOL 1介导的裂解的不同抗性机制。而T. B.罗德西亚原虫的抗性与血清抗性相关蛋白（SRA）的表达有关，该蛋白与寄生虫溶酶体内的APOL 1相互作用，抑制其溶解作用; B.冈比亚的抗性是由寄生虫HpHb受体的表达减少控制的，限制了锥虫对APOL 1的吸收。基于最后的观察，我们假设宿主APOL 1环境的变化可以显著改变T。B.冈比亚生长，从而抵抗/易感昏睡病。为了检验这一假设，我们测量了HAT患者、未感染的地方病对照和血清学阳性受试者（SERO TL+）的血液APOL 1相对表达，这些受试者被怀疑将感染控制到该领域使用的现有检测无法检测到的寄生虫学水平。所有的RNA样品都是从几内亚沿海HAT红树林疫源地的医学调查中获得的。结果表明，APOL 1的表达是一个复杂的性状依赖于各种因素，需要考虑在分析中。然而，多变量分析显示，与地方病对照相比，HAT和SERO TL+受试者中的APOL 1表达水平显著更高（p = 0.006）。这一结果表明，T. B.冈比亚，但不相关的电阻/易感性在其人类宿主。(c)2012爱思唯尔有限公司版权所有。
Most African trypanosome species are sensitive to trypanolytic factors (TLFs) present in human serum. Trypanosome lysis was demonstrated to be associated with apolipoprotein L-1 (APOL1). Trypanosoma brucei (T. b.) gambiense and Trypanosoma brucei rhodesiense, the two human infective trypanosome species, have both developed distinct resistance mechanisms to APOL1 mediated lysis. Whereas T. b. rhodesiense resistance is linked with the expression of the serum resistance associated (SRA) protein that interacts with APOL1 inside the parasite lysosome, inhibiting its lytic action; T. b. gambiense resistance is rather controlled by a reduced expression of the parasite HpHb receptor, limiting APOL1 absorption by trypanosomes. Based on this last observation we hypothesised that variation in the host APOL1 environment could significantly alter T. b. gambiense growth and thus resistance/susceptibility to sleeping sickness. To test this hypothesis, we have measured blood APOL1 relative expression in HAT patients, uninfected endemic controls and serologically positive subjects (SERO TL+) that are suspected to control infection to parasitological levels that are undetectable by the available test used in the field. All RNA samples were obtained from medical surveys led in the HAT mangrove foci of Coastal Guinea. Results indicate that APOL1 expression is a complex trait dependant on a variety of factors that need to be taken into account in the analysis. Nevertheless, multivariate analysis showed that APOL1 expression levels were significantly higher in both HAT and SERO TL+ subject as compared to endemic controls (p = 0.006). This result suggests that APOL1 expression is likely induced by T. b. gambiense, but is not related to resistance/susceptibility in its human host. (c) 2012 Elsevier B.V. All rights reserved.