| Author | Forrester, Sarah | |
| Author | Goundry, Amy Louise | |
| Author | Leal, Bruna Torres Dias | |
| Author | Calvo, Thyago Leal | |
| Author | Moraes, Milton Ozório | |
| Author | Kaye, Paul M. | |
| Author | Mottram, Jeremy C. | |
| Author | Lima, Ana Paula Cabral de Araujo | |
| Access date | 2022-08-10T13:46:24Z | |
| Available date | 2022-08-10T13:46:24Z | |
| Document date | 2022 | |
| Citation | FORRESTER, Sarah et al. Tissue specific dual RNA-seq defines host–parasite interplay in murine visceral leishmaniasis caused by Leishmania donovani and Leishmania infantum. Microbiology Spectrum, v. 10, n. 2, p. 1-19, 6 Apr. 2022. | |
| ISSN | 2165-0497 | |
| URI | https://www.arca.fiocruz.br/handle/icict/54563 | |
| Description | Produção científica do Laboratório de Hanseníase. | pt_BR |
| Description | 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-by-side 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. | en_US |
| Sponsorship | This work was funded by a National Centre for Replacement, Refinement and Reduction of Animal in Research (NC3Rs)/Innovate UK CRACKIT Challenge Award (NC.CO13117 and NC/CO13295 to Paul M. Kaye and Jeremy C. Mottram). | |
| Sponsorship | Medical Research Council Newton (MR/M026167/1 and MR/N017269/1 to Jeremy C. Mottram, Paul M. Kaye, and Ana Paula Cabral de Araujo Lima). | |
| Sponsorship | Paul M. Kaye was supported by a Wellcome Trust Senior Investigator Award (WT104726). | |
| Sponsorship | Ana Paula Cabral de Araujo Lima was supported by FAPERJ (grant number E26/202.655/2019) and CNPq (grant number 311208/2017-7) and is a CNPq fellow. | |
| Language | eng | en_US |
| Publisher | American Society for Microbiology | |
| Rights | open access | |
| Title | Tissue specific dual RNA-seq defines host–parasite interplay in murine visceral leishmaniasis caused by Leishmania donovani and Leishmania infantum | en_US |
| Type | Article | |
| DOI | 10.1128/spectrum.00679-22 | |
| Abstract | 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 IFNγ 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 IL1β 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 IFNγ 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. | en_US |
| Affilliation | University of York. York Biomedical Research Institute. Department of Biology. York, England, United Kingdom. | |
| Affilliation | University of York. York Biomedical Research Institute. Department of Biology. York, England, United Kingdom / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | University of York. Hull York Medical School. York Biomedical Research Institute. York, England, United Kingdom. | |
| Affilliation | University of York. York Biomedical Research Institute. Department of Biology. York, England, United Kingdom. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | |
| Subject | Leishmania | en_US |
| Subject | RNAseq | en_US |
| Subject | Leishmaniasis | en_US |
| Subject | Mouse | en_US |
