Abstract

Background

Interleukin-10 (IL-10) has been implicated as the major cytokine responsible for the modulation of parasite-specific responses in filarial infections; however, the role of other IL-10 superfamily members in filarial infection is less well studied.

Methods

Peripheral blood mononuclear cells from loiasis patients were stimulated with or without filarial antigen. Cytokine production was quantified using a Luminex platform and T-cell expression patterns were assessed by flow cytometry.

Results

All patients produced significant levels of IL-10, IL-13, IL-5, IL-4, and IL-9 in response to filarial antigen, indicating a common infection-driven response. When comparing microfilaria (mf)-positive and mf-negative patients, there were no significant differences in spontaneous cytokine nor in parasite-driven IL-10, IL-22, or IL-28a production. In marked contrast, mf-positive individuals had significantly increased filarial antigen-driven IL-24 and IL-19 compared to mf-negative subjects. mf-positive patients also demonstrated significantly higher frequencies of T cells producing IL-19 in comparison to mf-negative patients. T-cell expression of IL-19 and IL-24 was positively regulated by IL-10 and IL-1β. IL-24 production was also regulated by IL-37.

Conclusion

These data provide an important link between IL-10 and its related family members IL-19 and IL-24 in the modulation of the immune response in human filarial infections.

Clinical Trials Registration

NCT00001230.

中文翻译：

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IL-10 及其相关超家族成员 IL-19 和 IL-24 在 Loa loa 感染中提供平行/冗余免疫调节

摘要

背景

白细胞介素 10 (IL-10) 被认为是负责调节丝虫感染中寄生虫特异性反应的主要细胞因子。然而，其他 IL-10 超家族成员在丝虫感染中的作用研究较少。

方法

来自loiasis 患者的外周血单核细胞用或不用丝虫抗原刺激。使用 Luminex 平台量化细胞因子的产生，并通过流式细胞术评估 T 细胞表达模式。

结果

所有患者在响应丝虫抗原时均产生显着水平的 IL-10、IL-13、IL-5、IL-4 和 IL-9，表明是常见的感染驱动反应。在比较微丝蚴 (mf) 阳性和 mf 阴性患者时，自发细胞因子和寄生虫驱动的 IL-10、IL-22 或 IL-28a 产生没有显着差异。形成鲜明对比的是，与 mf 阴性受试者相比，mf 阳性个体的丝虫抗原驱动的 IL-24 和 IL-19 显着增加。与 mf 阴性患者相比，mf 阳性患者还表现出显着更高的 T 细胞产生 IL-19 的频率。IL-19 和 IL-24 的 T 细胞表达受到 IL-10 和 IL-1β 的正调节。IL-24 的产生也受 IL-37 的调控。

结论

这些数据提供了 IL-10 及其相关家族成员 IL-19 和 IL-24 在调节人类丝虫感染免疫反应方面的重要联系。

临床试验注册

NCT00001230。