The likelihood of being bitten by sand flies infected with Leishmania (L.) donovani is considered to be high for all inhabitants living in the endemic areas, but only a small ratio of the population develop symptomatic visceral leishmanisis (VL). Since adequate activation of antimicrobial immune response plays a key role in control of pathogens early after infection we hypothesized that a dysfunction of essential cells of the immune system is associated with disease development after infection with L. donovani. In order to obtain insights into the capacity of leukocytes to respond to L. donovani, a whole blood based assay was applied to evaluate the production of cytokines and chemokines in clinical VL versus Ethiopian endemic healthy control (EHC). In response to L. donovani, VL blood cultures showed significantly lower secretion of IL-12p70, IL-6, IL-17, IL-8 and IP-10 compared to EHC. On the contrary, there was a significantly higher secretion of IL-10 observed in VL compared to EHC. In response to LPS also a lower IL-1β, IL-12p70 and IL-6 secretion was observed in VL as compared to EHC. The data clearly indicate a diminished ability of blood leukocytes in VL to respond to L. donovani and to the TLR ligand LPS. This compromised response in VL may contribute to the severe disease development and enhanced susceptibility to secondary infections in VL.

中文翻译：

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基于全血的体外培养显示内脏利什曼病中促炎细胞因子和趋化因子的分泌减少

对于生活在流行区的所有居民来说，被多诺瓦尼利什曼原虫 (L.) 感染的白蛉叮咬的可能性被认为很高，但只有一小部分人口会出现症状性内脏利什曼病 (VL)。由于充分激活抗微生物免疫反应在感染后早期控制病原体中起关键作用，我们假设免疫系统基本细胞的功能障碍与多诺瓦尼乳杆菌感染后的疾病发展有关。为了深入了解白细胞对多诺瓦尼乳杆菌的反应能力，应用基于全血的测定来评估临床 VL 与埃塞俄比亚地方病健康对照 (EHC) 中细胞因子和趋化因子的产生。响应 L. donovani，VL 血培养显示 IL-12p70 的分泌显着降低，与 EHC 相比，IL-6、IL-17、IL-8 和 IP-10。相反，与 EHC 相比，在 VL 中观察到的 IL-10 分泌明显更高。与 EHC 相比，在响应 LPS 时，在 VL 中也观察到较低的 IL-1β、IL-12p70 和 IL-6 分泌。数据清楚地表明 VL 中的血液白细胞对多诺瓦尼乳杆菌和 TLR 配体 LPS 的反应能力降低。VL 中这种受损的反应可能导致严重的疾病发展和 VL 对继发感染的易感性增加。donovani 和 TLR 配体 LPS。VL 中这种受损的反应可能导致严重的疾病发展和 VL 对继发感染的易感性增加。donovani 和 TLR 配体 LPS。VL 中这种受损的反应可能导致严重的疾病发展和 VL 对继发感染的易感性增加。