title: Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens.
abstract: Organisms typically face infection by diverse pathogens, and hosts are thought to have developed specific responses to each type of pathogen they encounter. The advent of transcriptomics now makes it possible to test this hypothesis and compare host gene expression responses to multiple pathogens at a genome-wide scale. Here, we performed a meta-analysis of multiple published and new transcriptomes using a newly developed bioinformatics approach that filters genes based on their expression profile across datasets. Thereby, we identified common and unique molecular responses of a model host species, the honey bee (Apis mellifera), to its major pathogens and parasites: the Microsporidia Nosema apis and Nosema ceranae, RNA viruses, and the ectoparasitic mite Varroa destructor, which transmits viruses.
  
  
  
  We identified a common suite of genes and conserved molecular pathways that respond to all investigated pathogens, a result that suggests a commonality in response mechanisms to diverse pathogens. We found that genes differentially expressed after infection exhibit a higher evolutionary rate than non-differentially expressed genes. Using our new bioinformatics approach, we unveiled additional pathogen-specific responses of honey bees; we found that apoptosis appeared to be an important response following microsporidian infection, while genes from the immune signalling pathways, Toll and Imd, were differentially expressed after Varroa/virus infection. Finally, we applied our bioinformatics approach and generated a gene co-expression network to identify highly connected (hub) genes that may represent important mediators and regulators of anti-pathogen responses.
  
  
  
  Our meta-analysis generated a comprehensive overview of the host metabolic and other biological processes that mediate interactions between insects and their pathogens. We identified key host genes and pathways that respond to phylogenetically diverse pathogens, representing an important source for future functional studies as well as offering new routes to identify or generate pathogen resilient honey bee stocks. The statistical and bioinformatics approaches that were developed for this study are broadly applicable to synthesize information across transcriptomic datasets. These approaches will likely have utility in addressing a variety of biological questions.
authors.affiliation: German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany. vincent.bs.doublet@gmail.com.|Centre for Ecology and Conservation, University of Exeter, Penryn, UK. vincent.bs.doublet@gmail.com.
authors.forename: Vincent
authors.identifier: 0000-0002-6313-1222
authors.initials: V
authors.lastname: Doublet
authors.affiliation: German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.|Institute of Computer Science, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Poeschl
authors.affiliation: German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.|Institute of Computer Science, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.|Technische Hochschule Mittelhessen, Gießen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gogol-Döring
authors.affiliation: INRA, UR 406 Abeilles et Environnement, Avignon, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Alaux
authors.affiliation: Dipartimento di Scienze AgroAlimentari, Ambientali e Animali, Università degli Studi di Udine, Udine, Italy.
authors.forename: Desiderato
authors.initials: D
authors.lastname: Annoscia
authors.affiliation: Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania.
authors.forename: Christian
authors.initials: C
authors.lastname: Aurori
authors.affiliation: Department of Biology, East Carolina University, Greenville, NC, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Barribeau
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, State College, PA, USA.|Present address: MRC IGMM, University of Edinburgh, Western General Hospital, Edinburgh, UK.|Present address: MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
authors.forename: Oscar C
authors.initials: OC
authors.lastname: Bedoya-Reina
authors.affiliation: School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, UK.
authors.forename: Mark J F
authors.initials: MJ
authors.lastname: Brown
authors.affiliation: Department of Biosciences, Swansea University, Swansea, UK.
authors.forename: James C
authors.initials: JC
authors.lastname: Bull
authors.affiliation: Department of Plant Sciences and Plant Pathology, Montana State University, Bozeman, MT, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Flenniken
authors.affiliation: Department of Entomology, Center for Pollinator Research, Pennsylvania State University, State College, PA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Galbraith
authors.affiliation: Department of Molecular Microbiology and Bee Diseases, Institute for Bee Research, Hohen Neuendorf, Germany.|Department of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Genersch
authors.affiliation: Department of Molecular Microbiology and Bee Diseases, Institute for Bee Research, Hohen Neuendorf, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gisder
authors.affiliation: German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.|Institute of Computer Science, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Grosse
authors.affiliation: Department of Entomology, Center for Pollinator Research, Pennsylvania State University, State College, PA, USA.|Department of Fisheries, Wildlife, and Conservation Biology, The Monarch Joint Venture, University of Minnesota, St. Paul, MN, USA.
authors.forename: Holly L
authors.initials: HL
authors.lastname: Holt
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Hultmark
authors.affiliation: German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.|Institute for Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.|Present address: International Centre of Insect Physiology and Ecology (icipe), Environmental Health Theme, Nairobi, Kenya.
authors.forename: H Michael G
authors.initials: HM
authors.lastname: Lattorff
authors.affiliation: INRA, UR 406 Abeilles et Environnement, Avignon, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Conte
authors.affiliation: School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, UK.
authors.forename: Fabio
authors.initials: F
authors.lastname: Manfredini
authors.affiliation: Institute for Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.|School of Biological Sciences, Queen's University Belfast, Belfast, UK.|Institute of Biology, Freie Universität Berlin, Berlin, Germany.|Department for Materials and Environment, BAM Federal Institute for Materials Research and Testing, Berlin, Germany.
authors.forename: Dino P
authors.initials: DP
authors.lastname: McMahon
authors.affiliation: German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.|Institute for Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Robin F A
authors.initials: RF
authors.lastname: Moritz
authors.affiliation: Dipartimento di Scienze AgroAlimentari, Ambientali e Animali, Università degli Studi di Udine, Udine, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nazzi
authors.affiliation: Department of Entomology, Center for Pollinator Research, Pennsylvania State University, State College, PA, USA.|Department of Entomology and Nematology, University of California, Davis, CA, USA.
authors.forename: Elina L
authors.initials: EL
authors.lastname: Niño
authors.affiliation: German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.|Department of Computer Science, TFome Research Group, Bioinformatics Group, Interdisciplinary Center of Bioinformatics, University of Leipzig, Leipzig, Germany.|Paul-Flechsig-Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Nowick
authors.affiliation: Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: van Rij
authors.affiliation: German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.|Institute for Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.|School of Biological Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Paxton
authors.affiliation: Department of Entomology, Center for Pollinator Research, Pennsylvania State University, State College, PA, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Grozinger
mesh_terms: D000818:Animals; D001516:Bees / Q000235:genetics* / Q000382:microbiology / Q000469:parasitology / Q000821:virology; D030541:Databases, Genetic; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D054884:Host-Pathogen Interactions / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D058977:Molecular Sequence Annotation; D016818:Nosema / Q000502:physiology; D012328:RNA Viruses / Q000502:physiology; D057077:Varroidae / Q000502:physiology
keywords: Apis mellifera; Co-expression network; DWV; IAPV; Immunity; Meta-analysis; Nosema; RNA virus; Transcriptomics; Varroa destructor