title: Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions.
abstract: BACKGROUND
  Parasites 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA. dillonl@umd.edu.|Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, 20742, USA. dillonl@umd.edu.
authors.forename: Laura A L
authors.initials: LA
authors.lastname: Dillon
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA. srahul@umd.edu.
authors.forename: Rahul
authors.initials: R
authors.lastname: Suresh
authors.affiliation: Department of Mathematics, University of Maryland, College Park, MD, 20742, USA. kwame.okrah@gmail.com.
authors.forename: Kwame
authors.initials: K
authors.lastname: Okrah
authors.affiliation: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, 20742, USA. hcorrada@gmail.com.|Department of Computer Science, University of Maryland, College Park, MD, 20742, USA. hcorrada@gmail.com.
authors.forename: Hector
authors.initials: H
authors.lastname: Corrada Bravo
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA. dmosser@umd.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Mosser
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA. elsayed@umd.edu.|Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, 20742, USA. elsayed@umd.edu.|Present Address: 3128 Bioscience Research Bldg., University of Maryland, College Park, MD, 20742, USA. elsayed@umd.edu.
authors.forename: Najib M
authors.initials: NM
authors.lastname: El-Sayed
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000235:genetics*; D018320:Leishmania major / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D059467:Transcriptome / Q000235:genetics