Genome assembly and transcriptome analysis provide insights into the anti-schistosome mechanism of Microtus fortis

Abstract Microtus fortis (M. fortis) is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection. However, the underlying molecular mechanisms of this resistance are not yet known. Here, we performed the first de novo genome assembly of M. fortis, comprehensive gene annotation and evolution analysis. Furthermore, we compared the recovery rate of schistosomes, pathological changes and liver transcriptomes between M. fortis and mice at different time points after infection. We observed that the time and type of immune response in M. fortis were different from those in mice. M. fortis activated immune and inflammatory responses on the 10th day post infection, such as leukocyte extravasation, antibody activation, Fc-gamma receptor-mediated phagocytosis, and the interferon signalling cascade, which played important roles in preventing the development of schistosomes. In contrast, an intense immune response occurred in mice at the late stages of infection and could not eliminate schistosomes. Infected mice suffered severe pathological injury and continuous decreases in cell cycle, lipid metabolism and other functions. Our findings offer new insights into the intrinsic resistance mechanism of M. fortis against schistosome infection. The genome sequence also provides bases for future studies of other important traits in M. fortis.