Transcriptional profiling of Microtus fortis responses to S. japonicum: New sight into Mf-Hsp90α resistance mechanism

Abstract

Aims: Schistosomiasis is a parasitic disease with a chronic debilitating character caused by parasitic flatworms of the genus Schistosoma. The main disease-causing species of Schistosoma in China is S. japonicum. M fortis has been proved to be a nonpermissive host of S. japonicum. Mf-HSP90α (Microtus fortis heat shock protein 90alpha), the homologue of HSP90α, display anti-schistosome effect in vitro and in vivo. In the current study, in order to investigate the mechanism of anti-schistosome effect of Mf-HSP90α, we conducted RNA-Seq to obtain the transcriptome profile of M. fortis liver infected with S. japonicum at different time points.

Methods and results: By mapping the differential expressed genes (DEGs) to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the JAK2/STAT1 pathway was highly enriched with an elevated level of IL-10 and HSP90α. We then checked the IL-10-JAK2/STAT1-HSP90α pathway, and found that this pathway was activated in the infected mice with S. japonicum. The expression of the molecules in this pathway was elevated on the 10^th day after infection and gradually decreased on the 20^th day.

Conclusions: The IL-10-JAK2/STAT1-HSP90α axis was associated with the anti-schistosome effect of Mf-HSP90α, and targeting IL-10-JAK2/STAT1-HSP90α axis might be a novel therapeutic strategy for developing resistance to S. japonicum infection.

Keywords: Microtus fortis; Schistosoma japonicum; HSP90α; IL-10-JAK2/STAT1; RNA-Seq.