Centre International de Recherche-Développement sur l'Elevage en zone Subhumide, 01 BP 454 Bobo-Dioulasso 01, Burkina Faso.
Infect Genet Evol. 2012 Oct;12(7):1519-23. doi: 10.1016/j.meegid.2012.05.010. Epub 2012 Jun 9.
Most African trypanosome species are sensitive to trypanolytic factors (TLFs) present in human serum. Trypanosome lysis was demonstrated to be associated with apolipoprotein L-I (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.
大多数非洲锥虫物种对人血清中存在的溶锥虫因子（TLFs）敏感。锥虫溶解被证明与载脂蛋白 L-I（APOL1）有关。布氏锥虫（T. b.）冈比亚亚种和布氏锥虫罗得西亚亚种，这两种人类感染的锥虫物种，都已经发展出对 APOL1 介导的溶解的独特抗性机制。虽然 T. b. rhodesiense 的抗性与血清抗性相关（SRA）蛋白的表达有关，该蛋白在寄生虫溶酶体内部与 APOL1 相互作用，抑制其溶解作用；但 T. b. gambiense 的抗性则是通过寄生虫 HpHb 受体的表达减少来控制的，从而限制了锥虫对 APOL1 的吸收。基于这最后一个观察结果，我们假设宿主 APOL1 环境的变化可能会显著改变 T. b. gambiense 的生长，从而改变对昏睡病的抗性/敏感性。为了验证这一假设，我们测量了 HAT 患者、未感染的地方病对照者和血清学阳性者（SERO TL(+)）的血液 APOL1 相对表达，这些人怀疑控制感染到寄生虫水平，而这些水平是目前在现场使用的可用检测方法无法检测到的。所有 RNA 样本均来自在沿海几内亚的 HAT 红树林焦点进行的医学调查。结果表明，APOL1 表达是一种复杂的特征，取决于各种因素，在分析中需要考虑这些因素。然而，多变量分析表明，HAT 和 SERO TL(+)患者的 APOL1 表达水平明显高于地方病对照者（p=0.006）。这一结果表明，APOL1 表达可能是由 T. b. gambiense 诱导的，但与人类宿主的抗性/敏感性无关。
