1Department of Zoology (Centre for Advanced Studies), Visva-Bharati University, Santiniketan, 731235 India.
2Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et immuno-intervention thérapeutique, Sorbonne Universités, F-75006 Paris, France.
Commun Biol. 2019 May 7;2:169. doi: 10.1038/s42003-019-0392-8. eCollection 2019.
Interaction between innate immune cells and parasite plays a key role in the immunopathogenesis of lymphatic filariasis. Despite being professional antigen presenting cells critical for the pathogen recognition, processing and presenting the antigens for mounting T cell responses, the dendritic cell response and its role in initiating CD4 T cell response to filaria, in particular , the most prevalent microfilaria is still not clear. Herein, we demonstrate that a 70 kDa phosphorylcholine-binding sheath antigen induces human dendritic cell maturation and secretion of several pro-inflammatory cytokines. Further, microfilarial sheath antigen-stimulated dendritic cells drive predominantly Th1 and regulatory T cell responses while Th17 and Th2 responses are marginal. Mechanistically, sheath antigen-induced dendritic cell maturation, and Th1 and regulatory T cell responses are mediated via toll-like receptor 4 signaling. Our data suggest that sheath antigen exploits dendritic cells to mediate distinct CD4 T cell responses and immunopathogenesis of lymphatic filariasis.
先天免疫细胞与寄生虫之间的相互作用在淋巴丝虫病的免疫发病机制中起着关键作用。尽管树突状细胞是专业的抗原呈递细胞，对于病原体的识别、加工和呈递抗原以引发 T 细胞反应至关重要，但树突状细胞的反应及其在启动对丝虫，特别是最常见的微丝蚴的 CD4 T 细胞反应中的作用仍不清楚。在此，我们证明了一种 70 kDa 的磷酸胆碱结合鞘抗原可诱导人树突状细胞成熟并分泌几种促炎细胞因子。此外，微丝蚴鞘抗原刺激的树突状细胞主要驱动 Th1 和调节性 T 细胞反应，而 Th17 和 Th2 反应则微不足道。从机制上讲，鞘抗原诱导的树突状细胞成熟和 Th1 和调节性 T 细胞反应是通过 Toll 样受体 4 信号传导介导的。我们的数据表明，鞘抗原利用树突状细胞来介导淋巴丝虫病的不同 CD4 T 细胞反应和免疫发病机制。
