Tissue Specific Dual RNA-Seq Defines Host–Parasite Interplay in Murine Visceral Leishmaniasis Caused by Leishmania donovani and Leishmania infantum

Forrester, Sarah; Goundry, Amy; Dias, Bruna T.; Leal-Calvo, Thyago; Moraes, Milton Ozório; Kaye, Paul M.; Mottram, Jeremy C.; Lima, Ana Paula

doi:10.1128/spectrum.00679-22

Cited by 14 publications

(6 citation statements)

References 64 publications

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“…Previously, bulk RNAseq has been employed to explore transcriptional changes in the cells of infected hosts as opposed to non-infected animals as well as the transcriptome of the parasite (Forrester et al, 2022). But due to the intrinsic limitations of the bulk nature of the technology, the relation between the differentially expressed genes and the parasitized cells is a task yet to be solved.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies with various species of Leishmania applied bulk RNA-seq methods to analyze drug resistance (Perea-Martínez et al, 2022), RNA interactome (Kalesh et al, 2022), host-parasite interactions (Dillon et al, 2015), and characterization of the developmental stages of L. major in the sand fly (Inbar et al, 2017). Dual RNA-Seq analysis that targeted both host and parasite transcriptomes by bulk RNA-seq in liver and spleen of L. donovani and L. infantum infected mouse models showed potential differences in the pathophysiology in the two infections (Forrester et al, 2022). Transcriptional analysis using in silico cell type deconvolution identified a gene expression signature that was conserved in VL cohorts in India, Ethiopia and Brazil (Dirkx et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Dual scRNA-Seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Karagiannis¹,

Gannavaram²,

Verma

et al. 2022

Preprint

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Although phagocytic cells are documented targets of Leishmania parasites, it is unclear whether these parasites can infect other cell types. In this study, we describe a computational approach that exploits scRNA-seq to simultaneously analyze the transcriptomic signatures of the host cell and to identify rare and uncommon cells that harbor Leishmania donovani in the spleen and bone marrow. Individual cells were annotated as parasitized based on the presence of L. donovani transcripts that were detected with high accuracy. This unbiased approach allowed identification of heterogenous parasitized cell populations that cannot be detected by conventional methods. Consistent with previous studies, analysis of spleen cells isolated from L. donovani infected mice revealed inflammatory monocytes as the dominant parasitized cells. In addition, megakaryocytes, basophils , and NK cells were found to be the rare cells infected in the spleen. Unexpectedly, hematopoietic stem cells (HSCs), not known to be phagocytic, were the dominant cells parasitized cell in the bone marrow. In addition, eosinophils, megakaryocytes, and basal cells were the rare bone marrow cells found to be infected. scRNA-seq analysis revealed known phagocytic receptors FcγR and CD93 are expressed on HSCs . In vitro studies using purified HSCs showed that these cells can phagocytize L. donovani. Parasitized HSCs were also detectable in the bone marrow of mouse infected with L donovani. . This unbiased dual scRNA-seq approach enables identification of rare and uncommon parasitized cells that could be involved in pathogenesis, persistence, and protective immunity. Further, such approach could be used to study pathogenesis of other infectious agents.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dual scRNA-Seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Karagiannis¹,

Gannavaram²,

Verma

et al. 2022

Preprint

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“…L. infantum and L. donovani are species that cause VL, which can be fatal if not treated. The main symptoms of VL are hepatosplenomegaly, anemia and bleeding, and weight loss (Forrester et al, 2022). L. mexicana and L. braziliensis are likely to cause CL and MCL, respectively.…”

Section: Leishmaniasismentioning

confidence: 99%

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

Scariot

Staneviciute

Zhu

et al. 2022

Front. Cell. Infect. Microbiol.

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Nanotechnology is revolutionizing many sectors of science, from food preservation to healthcare to energy applications. Since 1995, when the first nanomedicines started being commercialized, drug developers have relied on nanotechnology to improve the pharmacokinetic properties of bioactive molecules. The development of advanced nanomaterials has greatly enhanced drug discovery through improved pharmacotherapeutic effects and reduction of toxicity and side effects. Therefore, highly toxic treatments such as cancer chemotherapy, have benefited from nanotechnology. Considering the toxicity of the few therapeutic options to treat neglected tropical diseases, such as leishmaniasis and Chagas disease, nanotechnology has also been explored as a potential innovation to treat these diseases. However, despite the significant research progress over the years, the benefits of nanotechnology for both diseases are still limited to preliminary animal studies, raising the question about the clinical utility of nanomedicines in this field. From this perspective, this review aims to discuss recent nanotechnological developments, the advantages of nanoformulations over current leishmanicidal and trypanocidal drugs, limitations of nano-based drugs, and research gaps that still must be filled to make these novel drug delivery systems a reality for leishmaniasis and Chagas disease treatment.

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“…High quality reads were then aligned using STAR aligner v.2.7.10a [5] . Alignments were run using these combined parasite and human references using ––outFilterMatchNmin 40 to locally align to account for splice leader sequences within parasite transcripts, which may otherwise be discarded [6] . Other STAR alignment parameters as follows: –outFilterMultimapNmax 20 –outFilterMismatchNmax 15 –alignSJoverhangMin 8 –alignMatesGapMax 1000000 ––outFilterMatchNmin 40 –quantMode GeneCounts.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Dataset of dual RNA-seq mapping in visceral leishmaniasis: Inquiry on parasite transcripts in human blood transcriptome upon Leishmania infantum infection

et al. 2023

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Tissue Specific Dual RNA-Seq Defines Host–Parasite Interplay in Murine Visceral Leishmaniasis Caused by Leishmania donovani and Leishmania infantum

Cited by 14 publications

References 64 publications

Dual scRNA-Seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Dual scRNA-Seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

Dataset of dual RNA-seq mapping in visceral leishmaniasis: Inquiry on parasite transcripts in human blood transcriptome upon Leishmania infantum infection

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