Small particles of Echinococcus granulosus (spegs) and Echinococcus multilocularis (spems) promote follicular T helper cell expansion and are associated with IgE and IgG4 class switching in human lymph nodes

细粒棘球绦虫(小颗粒)和多房棘球绦虫(小颗粒)可促进滤泡辅助性T细胞扩增,并与人类淋巴结中的IgE和IgG4类别转换相关。

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Abstract

BACKGROUND: Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are zoonotic diseases caused by the larval stages of Echinococcus granulosus and E. multilocularis. Prior studies have identified small particles from the outer layer of parasitic lesions termed spegs (from E. granulosus) and spems (from E. multilocularis), which appear to interact with the human immune system, leading to lymph node enlargement. METHODS: We analyzed lymph nodes from CE (n = 3) and AE (n = 3) patients by immunohistochemical staining for spegs/spems and CD57. Automated image analysis revealed a significantly increased number of CD57-positive cells in Echinococcus particle-positive germinal centers compared with speg-/spem-negative germinal centers. Double immunofluorescence staining was used to characterize CD57-positive cells with markers for CD2, CD3, CD4, CD8, PD-1, Granzyme B, Perforin, and T-cell intracellular antigen 1 (TIA1). Additionally, IgG4 and IgE immunostaining was performed on liver lesions and lymph nodes containing spegs and spems and compared with unaffected controls. RESULTS: Spegs and spems were found to accumulate in the germinal centers of the lymph nodes. Affected germinal centers showed a higher number of CD57-positive cells, which coexpressed CD2, CD3, CD4, and PD-1 but lacked cytotoxic markers (CD8, Granzyme B, Perforin, TIA1), identifying them as follicular helper T cells (Tfh). Furthermore, the speg- and spem-affected liver and lymph node sections exhibited significantly increased numbers of IgG4-, IgE-, and CD57-positive cells. CONCLUSIONS: Spegs and spems are associated with changes in the host immune response, characterized by an increased accumulation of Tfh in germinal centers. This finding is accompanied by the presence of IgE and IgG4 plasma cells in the lymph node and the perilesional area, suggesting parasite-associated immunomodulatory processes in echinococcosis.

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