Dual transcriptome analyses of a non-healing chronic Leishmania donovani infection in mice

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Visceral leishmaniasis (VL) is caused by protozoan parasites of the genus Leishmania and is characterized by clinical manifestations including fever, hepatosplenomegaly, and anemia. We previously developed a non-healing chronic model of experimental VL, using BALB/c mice infected with Leishmania donovani , which manifest hepatosplenomegaly, leukopenia, and anemia. In mice, it is widely accepted that immune responses in the spleen and liver do not necessarily occur in parallel during experimental VL. This implies that Leishmania parasites may also exhibit different gene expression patterns in these distinct tissues. In this study, we performed dual transcriptome analyses of the spleen and liver from L. donovani -infected BALB/c mice to characterize tissue-specific responses of both the host and the parasite. Two independent transcriptome analyses with high reproducibility revealed tissue-specific expression patterns of host genes during L. donovani infection. For example, Pdilt was upregulated in the spleen but downregulated in the liver, whereas Marco displayed the opposite pattern. By contrast, gene expression patterns of L. donovani amastigotes were relatively conserved between the spleen and liver. These results suggest that tissue-specific host immune responses play a critical role in driving tissue-specific pathology, whereas they have limited influence on parasite gene expressions in this non-healing model of experimental VL.