Characterization of MicroRNA Cargo of Extracellular Vesicles Isolated From the Plasma of Schistosoma japonicum-Infected Mice

Abstract

Schistosoma is a genus of parasitic trematodes that undergoes complex migration in final hosts, finally developing into adult worms, which are responsible for egg production and disease dissemination. Recent studies documented the importance of extracellular vesicles (EVs) in the regulation of host-parasite interactions. Herein, we investigated the microRNA (miRNA) profiles of EVs isolated from host plasma at different stages of Schistosoma japonicum infection (lung stage: 3 days post-infection (dpi), and liver stages: 14 and 21 dpi) to identify miRNA cargo potentially involved in the pathogenesis and immune regulation of schistosomiasis. Characterization of the isolated plasma EVs revealed their diameter to be approximately 100 nm, containing typical EV markers such as Hsp70 and Tsg101. Deep sequencing analysis indicated the presence of 811 known and 15 novel miRNAs with an increasing number of differential miRNAs from the lung stage (27 miRNAs) to the liver stages (58 and 96 miRNAs at 14 and 21 dpi, respectively) in the plasma EVs of infected mice compared to EVs isolated from the uninfected control. In total, 324 plasma EV miRNAs were shown to be co-detected among different stages of infection and the validation of selected miRNAs showed trends of abundance similar to deep sequencing analysis. For example, miR-1a-3p and miR-122-5p showed higher abundance, whereas miR-150-3p and miR-126a showed lower abundance in the plasma EVs of infected mice at 3, 14, and 21 dpi as compared to those of uninfected mice. In addition, bioinformatic analysis combined with PCR validation of the miRNA targets, particularly those associated with the immune system and parasitic infectious disease, indicated a significant increase in the expression of Gbp7and Ccr5 in contrast to the decreased expression of Fermt3, Akt1, and IL-12a. Our results suggested that the abundance of miRNA cargo of the host plasma EVs was related to the stages of Schistosoma japonicum infection. Further studies on the roles of these miRNAs may reveal the regulatory mechanism of the host-parasite interaction. Moreover, the differentially abundant miRNA cargo in host EVs associated with S. japonicum infection may also provide valuable clues for identifying novel biomarkers for schistosomiasis diagnosis.

Roles of microRNAs and Long Non-Coding RNAs Encoded by Parasitic Helminths in Human Carcinogenesis

“…In this sense, distinct S. japonicum miRNAs were identified in extracellular vesicles from host serum, such asSja-let-7 and Sja-mir-190-5p, which were validated. Other non-validated miRNAs include Sja-mir-71a, Sja-mir-71b, Sja-mir-190-5p, Sja-let-7, and Sja-mir-36a [ 97 ]. Sja-bantam, Sja-mir-3479-3p, Sja-mir-10-5p, and Sja-mir-8185 were identified in the plasma of infected mice and rabbits [ 86 ].…”

Multifunctional Roles of MicroRNAs in Schistosomiasis

“…Human activities in infected water promotes transmission of schistosomiasis ( Lam et al, 2022 ). More than 230 million people in 78 tropical and subtropical countries are affected annually by schistosomiasis, which is the second most prevalent parasitic disease after malaria ( Li et al, 2022 ). Infections among travelers, migrants, and immigrants are also emerging in industrialized countries, which poses significant risks worldwide ( Lu et al, 2016 ).…”

“…Schistosomes have numerous naturally permissive hosts (such as 46 species for S. japonicum , including cattle, pigs, sheep, goats, and mice) and non-adaptive hosts (such as water buffalo, Rattus norvegicus , Microtus fortis , and immunodeficient mice). Comparative studies elucidating the miRNA expression profiles of different hosts infected different developmental stages of schistosomes were also conducted ( Yu X. et al, 2019 ; Sun et al, 2021 ; Tang et al, 2021 ; Li et al, 2022 ; Liu et al, 2022 ). The characterization of differentially expressed worm-derived or host-derived miRNAs can also be a supplementary tool for grading and diagnosis of schistosomiasis ( Cai et al, 2018 ; Mu et al, 2019 ; Cai et al, 2020 ).…”