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Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis

Shen, Jia; Zhao, Siyu; Peng, Mei; Li, Yanguo; Zhang, Lichao; Li, Xiaoping; Hu, Yunyi; Wu, Mingrou; Xiang, Suoyu; Wu, Xiaoying; Liu, Jiahua; Zhang, Beibei; Chen, Zebin; Lin, Datao; Liu, Huanyao; Tang, Wenyan; Chen, Jun; Sun, Xi; Liao, Qi; Hide, Geoff; Zhou, Zhijun; Lun, Zhao-Rong; Wu, Zhongdao

Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis Thumbnail


Authors

Jia Shen

Siyu Zhao

Mei Peng

Yanguo Li

Lichao Zhang

Xiaoping Li

Yunyi Hu

Mingrou Wu

Suoyu Xiang

Xiaoying Wu

Jiahua Liu

Beibei Zhang

Zebin Chen

Datao Lin

Huanyao Liu

Wenyan Tang

Jun Chen

Xi Sun

Qi Liao

Zhijun Zhou

Zhao-Rong Lun

Zhongdao Wu



Abstract

Schistosoma parasites, causing schistosomiasis, exhibit typical host specificity in host preference. Many mammals, including humans, are susceptible to infection, while the widely distributed rodent, Microtus fortis, exhibits natural anti-schistosome characteristics. The mechanisms of host susceptibility remain poorly understood. Comparison of schistosome infection in M. fortis with the infection in laboratory mice (highly sensitive to infection) offers a good model system to investigate these mechanisms and to gain an insight into host specificity. In this study, we showed that large numbers of leukocytes attach to the surface of human schistosomes in M. fortis but not in mice. Single-cell RNA-sequencing analyses revealed that macrophages might be involved in the cell adhesion, and we further demonstrated that M. fortis macrophages could be mediated to attach and kill schistosomula with dependence on Complement component 3 (C3) and Complement receptor 3 (CR3). Importantly, we provided direct evidence that M. fortis macrophages could destroy schistosomula by trogocytosis, a previously undescribed mode for killing helminths. This process was regulated by Ca2+/NFAT signaling. These findings not only elucidate a novel anti-schistosome mechanism in M. fortis but also provide a better understanding of host parasite interactions, host specificity and the potential generation of novel strategies for schistosomiasis control.

Citation

Shen, J., Zhao, S., Peng, M., Li, Y., Zhang, L., Li, X., …Wu, Z. (in press). Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis. Cell Discovery, 9(1), 101. https://doi.org/10.1038/s41421-023-00603-6

Journal Article Type Article
Acceptance Date Sep 13, 2023
Online Publication Date Oct 5, 2023
Deposit Date Oct 9, 2023
Publicly Available Date Oct 9, 2023
Journal Cell Discovery
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 9
Issue 1
Pages 101
DOI https://doi.org/10.1038/s41421-023-00603-6

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