| dc.description | Visceral leishmaniasis is associated with hepato-splenomegaly and altered
immune and hematological parameters in both preclinical animal models and humans.
We studied mouse experimental visceral leishmaniasis caused by Leishmania
infantum and Leishmania donovani in BALB/c mice using dual RNA-seq to investigate
the transcriptional response of host and parasite in liver and spleen. We
identified only 4 species-specific parasite expressed genes (SSPEGs; log2FC .1,
FDR ,0.05) in the infected spleen, and none in the infected liver. For the host
transcriptome, we found 789 differentially expressed genes (DEGs; log2FC .1,
FDR ,0.05) in the spleen that were common to both infections, with IFNg signaling
and complement and coagulation cascade pathways highly enriched, and an
additional 286 and 186 DEGs that were selective to L. donovani and L. infantum
infection, respectively. Among those, there were network interactions between
genes of amino acid metabolism and PPAR signaling in L. donovani infection and
increased IL1b and positive regulation of fatty acid transport in L. infantum infection,
although no pathway enrichment was observed. In the liver, there were
1,939 DEGs in mice infected with either L. infantum or L. donovani in comparison
to uninfected mice, and the most enriched pathways were IFNg signaling, neutrophil
mediated immunity, complement and coagulation, cytokine-chemokine
responses, and hemostasis. Additionally, 221 DEGs were selective in L. donovani
and 429 DEGs in L. infantum infections. These data show that the host response
for these two visceral leishmaniasis infection models is broadly similar, and ;10%
of host DEGs vary in infections with either parasite species. IMPORTANCE Visceral leishmaniasis (VL) is caused by two species of Leishmania
parasites, L. donovani in the Old World and L. infantum in the New World and
countries bordering the Mediterranean. Although cardinal features such as hepato-
splenomegaly and alterations in blood and immune function are evident, clinical
presentation may vary by geography, with for example severe bleeding often
associated with VL in Brazil. Although animal models of both L. donovani and L.
infantum have been widely used to study disease pathogenesis, a direct side-byside
comparison of how these parasites species impact the infected host and/or
how they might respond to the stresses of mammalian infection has not been
previously reported. Identifying common and distinct pathways to pathogenesis
will be important to ensure that new therapeutic or prophylactic approaches will
be applicable across all forms of VL. | |
