Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions

dc.contributor.authorDillon, Laura A. L.
dc.contributor.authorSuresh, Rahul
dc.contributor.authorOkrah, Kwame
dc.contributor.authorCorrada Bravo, Hector
dc.contributor.authorMosser, David M.
dc.contributor.authorEl-Sayed, Najib M.
dc.date.accessioned2021-08-17T13:55:48Z
dc.date.available2021-08-17T13:55:48Z
dc.date.issued2015-12-29
dc.description.abstractParasites of the genus Leishmania are the causative agents of leishmaniasis, a group of diseases that range in manifestations from skin lesions to fatal visceral disease. The life cycle of Leishmania parasites is split between its insect vector and its mammalian host, where it resides primarily inside of macrophages. Once intracellular, Leishmania parasites must evade or deactivate the host's innate and adaptive immune responses in order to survive and replicate. We performed transcriptome profiling using RNA-seq to simultaneously identify global changes in murine macrophage and L. major gene expression as the parasite entered and persisted within murine macrophages during the first 72 h of an infection. Differential gene expression, pathway, and gene ontology analyses enabled us to identify modulations in host and parasite responses during an infection. The most substantial and dynamic gene expression responses by both macrophage and parasite were observed during early infection. Murine genes related to both pro- and anti-inflammatory immune responses and glycolysis were substantially upregulated and genes related to lipid metabolism, biogenesis, and Fc gamma receptor-mediated phagocytosis were downregulated. Upregulated parasite genes included those aimed at mitigating the effects of an oxidative response by the host immune system while downregulated genes were related to translation, cell signaling, fatty acid biosynthesis, and flagellum structure. The gene expression patterns identified in this work yield signatures that characterize multiple developmental stages of L. major parasites and the coordinated response of Leishmania-infected macrophages in the real-time setting of a dual biological system. This comprehensive dataset offers a clearer and more sensitive picture of the interplay between host and parasite during intracellular infection, providing additional insights into how pathogens are able to evade host defenses and modulate the biological functions of the cell in order to survive in the mammalian environment.en_US
dc.description.urihttps://doi.org/10.1186/s12864-015-2237-2
dc.identifierhttps://doi.org/10.13016/moxz-9woz
dc.identifier.citationDillon, L.A.L., Suresh, R., Okrah, K. et al. Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions. BMC Genomics 16, 1108 (2015).en_US
dc.identifier.urihttp://hdl.handle.net/1903/27612
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isAvailableAtCollege of Computer, Mathematical & Natural Sciencesen_us
dc.relation.isAvailableAtPhysicsen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectLeishmaniaen_US
dc.subjectTranscriptomeen_US
dc.subjectRNA-seqen_US
dc.subjectDifferentiationen_US
dc.subjectHost-pathogen interactionsen_US
dc.subjectMacrophageen_US
dc.subjectMouseen_US
dc.titleSimultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactionsen_US
dc.typeArticleen_US

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