Clonorchis sinensis adult-derived proteins elicit Th2 immune responses by regulating dendritic cells via mannose receptor

作者：Lu Zhao, Mengchen Shi, Lina Zhou, Hengchang Sun, Xiaona Zhang, Lei He, Zeli Tang, Caiqin Wang, Yinjuan Wu, Tingjin Chen, Mei Shang, Xinyi Zhou, Zhipeng Lin, Xuerong Li, Xinbing Yu, Yan Huang · 发表于：PLoS neglected tropical diseases · 年份：2018 · DOI：10.1371/journal.pntd.0006251 · 被引用次数：23 · 研究领域：Parasites and Host Interactions、Liver physiology and pathology、Parasite Biology and Host Interactions

BACKGROUND: Clonorchis sinensis (C. sinensis) is the most widespread human liver fluke in East Asia including China and Korea. Clonorchiasis as a neglected tropical zoonosis, leads to serious economic and public health burden in China. There are considerable evidences for an etiological relation between chronic clonorchiasis and liver fibrosis in human beings. Liver fibrosis is a highly conserved and over-protected response to hepatic tissue injury. Immune cells including CD4+ T cell as well as dendritic cell (DC), and pro-fibrogenic cytokines like interleukin 4 (IL-4), IL-13 have been identified as vital manipulators in liver fibrogenesis. Our previous studies had a mere glimpse of T helper type 2 (Th2) dominant immune responses as key players in liver fibrosis induced by C. sinensis infection, but little is known about the involved mechanisms in this pathological process. METHODOLOGY/PRINCIPAL FINDINGS: By flow cytometry (FACS), adult-derived total proteins of C. sinensis (CsTPs) down-regulated the expression of surface markers CD80, CD86 and major histocompatibility complex class II (MHC-II) on lipopolysaccharide (LPS) induced DC. ELISA results demonstrated that CsTPs inhibited IL-12p70 release from LPS-treated bone marrow-derived dendritic cells (BMDC). IL-10 level increased in a time-dependent manner in LPS-treated BMDCs after incubation with CsTPs. CD4+ T cells incubated with LPS-treated BMDCs plus CsTPs could significantly elevate IL-4 level by ELISA. Meanwhile, elevat...