Spatiotemporal transcriptomic profiling reveals the dynamic immunological landscape of alveolar echinococcosis

作者：Zhihua Ou, Li Li, Peidi Ren, Tingting Zhou, Fan He, Jialing Chen, Huimin Cai, Xiumin Han, Yao-Dong Wu, Jiandong Li, Jiandong Li, Xiurong Li, Qiming Tan, Wenhui Li, Qi Chen, Nian‐Zhang Zhang, Xiuju He, Weigang Chen, Yanping Zhao, Jiwen Sun, Qian Zhang, Yan‐Tao Wu, Yingan Liang, Jie You, Guohai Hu, Xue‐Qi Tian, Sha Liao, Bao‐Quan Fu, Ao Chen, Xue‐Peng Cai, Huanming Yang, Jian Wang, Xin Jin, Xun Xu, Wan‐Zhong Jia, Junhua Li, Junhua Li, Hongbin Yan · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.04.04.577902 · 被引用次数：1 · 研究领域：Parasitic infections in humans and animals、Parasitic Infections and Diagnostics、Climate Change, Adaptation, Migration

ABSTRACT Alveolar echinococcosis (AE) is caused by the invasive growth of the metacestodes of Echinococcus multilocularis ( E. multilocularis ). The early diagnosis, management, and treatment of AE remains challenging. Herein, we integrated bulk RNA-seq, scRNA-seq, and ST technologies to reveal the immune characteristics both spatially and chronologically in E. multilocularis infected mouse liver. An unprecedented high-resolution spatial atlas of the E. multilocularis infection foci was obtained, revealing the pivotal role of neutrophils, Spp1 + monocyte-derived macrophages (MoMFs), and fibroblasts in AE progression. We observed continuous recruitment of neutrophils and macrophages into the infected tissues, indicating prolonged immune stimulation by the growing metacestodes. However, their spatial distribution patterns and functions changed during the infection cause. At the early infection stage, Il1b hi neutrophils aggregated in the lesion displayed the highest pattern-recognition receptor activity and may kill the metacestodes through NETosis, but their death in the infection foci might also trigger immune suppression. Meanwhile, Spp1 + MoMFs attached to the protoscoleces to clear the infection. At the late infection stage, the neutrophils failed to infiltrate into the lesion although their continuous recruitment into the infected liver. Even though the Spp1 + MoMFs enclosing the microcysts of E. multilocularis may retain their pathogen-killing ability, they may also prom...