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

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.

Spatiotemporal transcriptomic profiling reveals the dynamic immunological landscape of alveolar echinococcosis

“…Trogocytosis indicates a process in which one cell bites another cell, leading to the transfer of the cellular content of the target cell to the cell initiating the process, which can occur between multiple cell types 54 . Recent studies show that trogocytosis is involved in the killing of multicellular pathogens, for example, trogocytosis by macrophages kills Schistosoma japonicum and trogocytosis by neutrophils kills Trichomonas vaginalis 33,55 . We have tried to identify signals of trogocytosis, however, the associated gene expression levels varied greatly between samples, and we were unable to confirm the occurrence of trogocytosis during E. multilocularis infection.…”