Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
Burnet Institute, Melbourne, Victoria, Australia.
J Infect Dis. 2019 Jan 29;219(4):660-671. doi: 10.1093/infdis/jiy555.
The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs).
In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation. To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers.
CD16+ DCs underwent distinctive activation, with increased expression of maturation markers human leukocyte antigen (HLA)-DR and CD86, enhanced tumor necrosis factor (TNF) production, and coproduction of TNF/IL-10. In vitro restimulation with P falciparum further increased IL-10 production. In contrast, during naturally acquired malaria episode, CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function.
These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection. As dual cytokine producers, CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.
疟原虫寄生虫通过多种策略来颠覆宿主的免疫反应，包括调节树突状细胞（DC）。
在这项研究中，我们表明，疟原虫恶性疟原虫在体外将 CD16+DC 的细胞因子反应偏向于白细胞介素（IL）-10 的产生，与 Toll 样受体连接诱导的细胞因子谱明显不同。为了确定体内 CD16+DC 的反应性，我们评估了它们在疟疾初发志愿者中诱导的 P 恶性疟原虫感染后的功能。
CD16+DC 经历了独特的激活，其人类白细胞抗原（HLA）-DR 和 CD86 的成熟标志物表达增加，肿瘤坏死因子（TNF）的产生增强，以及 TNF/IL-10 的共产生。用 P 恶性疟原虫体外再刺激进一步增加了 IL-10 的产生。相比之下，在自然发生的疟疾发作期间，CD16+DC 显示出成熟度降低，这表明寄生虫负担增加和以前的暴露影响 DC 亚群的功能。
这些发现确定 CD16+DC 是在原发性人类疟原虫感染期间唯一被激活的 DC 亚群。作为双细胞因子产生物，CD16+DC 有助于炎症和调节性先天免疫过程。
