{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:45:37Z","timestamp":1791470737925,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010826","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000}}],"reference-count":95,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R00997X\/1"],"award-info":[{"award-number":["MR\/R00997X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/L018802\/2"],"award-info":[{"award-number":["MR\/L018802\/2"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["207467\/Z\/17\/Z"],"award-info":[{"award-number":["207467\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/R018839\/1"],"award-info":[{"award-number":["BB\/R018839\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/L020122\/2"],"award-info":[{"award-number":["BB\/L020122\/2"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["705930"],"award-info":[{"award-number":["705930"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001675","name":"International Brain Research Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001675","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Host behavioural changes are among the most apparent effects of infection. \u2018Sickness behaviour\u2019 can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here, using a real-time tracking and behavioural profiling platform, we show that in\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    , several systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in some lethal infections. Using multiple bacteria and\n                    <jats:italic>D<\/jats:italic>\n                    .\n                    <jats:italic>melanogaster<\/jats:italic>\n                    immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with\n                    <jats:italic>Micrococcus luteus<\/jats:italic>\n                    , a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the\n                    <jats:italic>Toll<\/jats:italic>\n                    ligand\n                    <jats:italic>sp\u00e4tzle<\/jats:italic>\n                    . In contrast, increased activity after infection with\n                    <jats:italic>Francisella novicida<\/jats:italic>\n                    , a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of both Toll and the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010826","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T13:46:32Z","timestamp":1663767992000},"page":"e1010826","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster"],"prefix":"10.1371","volume":"18","author":[{"given":"Crystal M.","family":"Vincent","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban J.","family":"Beckwith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina J.","family":"Simoes da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Pearson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Kierdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio F.","family":"Gilestro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-1750","authenticated-orcid":true,"given":"Marc S.","family":"Dionne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ppat.1010826.ref001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1006\/brbi.2000.0613","article-title":"Cytokine-induced sickness behavior: where do we stand?","volume":"15","author":"R. Dantzer","year":"2001","journal-title":"Brain Behav Immun"},{"key":"ppat.1010826.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ajpa.22698","article-title":"Human sickness behavior: Ultimate and proximate explanations","volume":"157","author":"EC Shattuck","year":"2015","journal-title":"American Journal of Physical Anthropology"},{"key":"ppat.1010826.ref003","first-page":"371","article-title":"Infectious diseases and social distancing in nature","author":"S Stockmaier","year":"2021","journal-title":"Science"},{"key":"ppat.1010826.ref004","doi-asserted-by":"crossref","first-page":"e62269","DOI":"10.1371\/journal.pone.0062269","article-title":"Discriminating fever behavior in house flies","volume":"8","author":"RD Anderson","year":"2013","journal-title":"PLoS One"},{"key":"ppat.1010826.ref005","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.50559","article-title":"Peptidoglycan-dependent NF-\u03baB activation in a small subset of brain octopaminergic neurons controls female oviposition","volume":"8","author":"A Masuzzo","year":"2019","journal-title":"Elife"},{"key":"ppat.1010826.ref006","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s00114-013-1057-y","article-title":"Context dependency and generality of fever in insects","volume":"100","author":"ZR Stahlschmidt","year":"2013","journal-title":"Naturwissenschaften"},{"key":"ppat.1010826.ref007","first-page":"1774","article-title":"Pathogen-induced food evasion behavior in Drosophila larvae","volume":"220","author":"S Surendran","year":"2017","journal-title":"J Exp Biol"},{"key":"ppat.1010826.ref008","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/19336934.2016.1207029","article-title":"Infection avoidance behavior: Viral exposure reduces the motivation to forage in female Drosophila melanogaster","volume":"11","author":"PF Vale","year":"2017","journal-title":"Fly (Austin)"},{"key":"ppat.1010826.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1242\/jeb.082511","article-title":"Neural parasitology: how parasites manipulate host behaviour","volume":"216","author":"SA Adamo","year":"2013","journal-title":"Journal of Experimental Biology"},{"key":"ppat.1010826.ref010","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1098\/rspb.2000.1182","article-title":"Fatal attraction in rats infected with Toxoplasma gondii","volume":"267","author":"M Berdoy","year":"2000","journal-title":"Proceedings of the Royal Society of London Series B: Biological Sciences"},{"key":"ppat.1010826.ref011","doi-asserted-by":"crossref","DOI":"10.3389\/fevo.2016.00080","article-title":"Host Manipulation by Parasites: Cases, Patterns, and Remaining Doubts","volume":"4","author":"M. Heil","year":"2016","journal-title":"Front Ecol Evol"},{"key":"ppat.1010826.ref012","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0031-9384(03)00163-X","article-title":"Parasite manipulation of the proximate mechanisms that mediate social behavior in vertebrates","volume":"79","author":"SL Klein","year":"2003","journal-title":"Physiol Behav"},{"key":"ppat.1010826.ref013","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1242\/jeb.073668","article-title":"Comparing mechanisms of host manipulation across host and parasite taxa","volume":"216","author":"KD Lafferty","year":"2013","journal-title":"Journal of Experimental Biology"},{"key":"ppat.1010826.ref014","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0149-7634(88)80004-6","article-title":"Biological basis of the behavior of sick animals","volume":"12","author":"BL Hart","year":"1988","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"ppat.1010826.ref015","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0165-2427(02)00069-7","article-title":"The concept of sickness behavior: a brief chronological account of four key discoveries","volume":"87","author":"RW Johnson","year":"2002","journal-title":"Vet Immunol Immunopathol"},{"key":"ppat.1010826.ref016","doi-asserted-by":"crossref","first-page":"e1000150","DOI":"10.1371\/journal.pbio.1000150","article-title":"The Role of Anorexia in Resistance and Tolerance to Infections in Drosophila","volume":"7","author":"JS Ayres","year":"2009","journal-title":"PLoS Biol"},{"key":"ppat.1010826.ref017","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.5665\/sleep.3764","article-title":"Increased Sleep Promotes Survival during a Bacterial Infection in Drosophila","volume":"37","author":"T-H Kuo","year":"2014","journal-title":"Sleep"},{"key":"ppat.1010826.ref018","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.anbehav.2009.10.001","article-title":"Crickets groom to avoid lethal parasitoids","volume":"79","author":"CM Vincent","year":"2010","journal-title":"Animal Behaviour"},{"key":"ppat.1010826.ref019","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.cell.2016.07.026","article-title":"Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation","volume":"166","author":"A Wang","year":"2016","journal-title":"Cell"},{"key":"ppat.1010826.ref020","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1086\/603640","article-title":"The Life of a Dead Ant: The Expression of an Adaptive Extended Phenotype","volume":"174","author":"SB Andersen","year":"2009","journal-title":"The American Naturalist"},{"key":"ppat.1010826.ref021","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/j.1365-2583.2006.00671.x","article-title":"\u2018Suicide\u2019 of crickets harbouring hairworms: a proteomics investigation","volume":"15","author":"DG Biron","year":"2006","journal-title":"Insect Molecular Biology"},{"key":"ppat.1010826.ref022","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1098\/rspb.2008.1597","article-title":"Parasite manipulation of brain monoamines in California killifish (Fundulus parvipinnis) by the trematode Euhaplorchis californiensis","volume":"276","author":"J c Shaw","year":"2009","journal-title":"Proceedings of the Royal Society B: Biological Sciences"},{"key":"ppat.1010826.ref023","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.beproc.2004.06.010","article-title":"Parasitic manipulation: where are we and where should we go?","volume":"68","author":"F Thomas","year":"2005","journal-title":"Behavioural Processes"},{"key":"ppat.1010826.ref024","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1046\/j.1420-9101.2002.00410.x","article-title":"Do hairworms (Nematomorpha) manipulate the water seeking behaviour of their terrestrial hosts?","volume":"15","author":"F Thomas","year":"2002","journal-title":"Journal of Evolutionary Biology"},{"key":"ppat.1010826.ref025","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1017\/S003118200007774X","article-title":"Effect of Toxoplasma gondii upon neophobic behaviour in wild brown rats, Rattus norvegicus","volume":"109","author":"JP Webster","year":"1994","journal-title":"Parasitology"},{"key":"ppat.1010826.ref026","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1152\/physrev.00010.2018","article-title":"The Sleep-Immune Crosstalk in Health and Disease","volume":"99","author":"L Besedovsky","year":"2019","journal-title":"Physiol Rev"},{"key":"ppat.1010826.ref027","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1471-2202-11-17","article-title":"Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NF\u03baB Relish","volume":"11","author":"T-H Kuo","year":"2010","journal-title":"BMC Neurosci"},{"key":"ppat.1010826.ref028","doi-asserted-by":"crossref","first-page":"R353","DOI":"10.1016\/j.cub.2007.03.049","article-title":"Interactions between circadian rhythm and immunity in Drosophila melanogaster","volume":"17","author":"MM Shirasu-Hiza","year":"2007","journal-title":"Current Biology"},{"key":"ppat.1010826.ref029","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.jaci.2005.08.005","article-title":"Links between the innate immune system and sleep","volume":"116","author":"JA Majde","year":"2005","journal-title":"J Allergy Clin Immunol"},{"key":"ppat.1010826.ref030","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1471-2148-9-8","article-title":"Sleeping to fuel the immune system: mammalian sleep and resistance to parasites","volume":"9","author":"MR Opp","year":"2009","journal-title":"BMC Evolutionary Biology"},{"key":"ppat.1010826.ref031","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nrn2576","article-title":"How (and why) the immune system makes us sleep","volume":"10","author":"L Imeri","year":"2009","journal-title":"Nat Rev Neurosci"},{"key":"ppat.1010826.ref032","doi-asserted-by":"crossref","first-page":"20190344","DOI":"10.1098\/rsbl.2019.0344","article-title":"Viral infection causes sex-specific changes in fruit fly social aggregation behaviour","volume":"15","author":"JA Siva-Jothy","year":"2019","journal-title":"Biology Letters"},{"key":"ppat.1010826.ref033","doi-asserted-by":"crossref","first-page":"e434","DOI":"10.7717\/peerj.434","article-title":"Immune stimulation reduces sleep and memory ability in Drosophila melanogaster","volume":"2","author":"EB Mallon","year":"2014","journal-title":"PeerJ"},{"key":"ppat.1010826.ref034","first-page":"3350","article-title":"Physiological and metabolic consequences of viral infection in Drosophila melanogaster","volume":"216","author":"PA Arnold","year":"2013","journal-title":"J Exp Biol"},{"key":"ppat.1010826.ref035","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cub.2007.12.054","article-title":"Circadian Regulation in the Ability of Drosophila to Combat Pathogenic Infections","volume":"18","author":"J-E Lee","year":"2008","journal-title":"Current Biology"},{"key":"ppat.1010826.ref036","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.imbio.2006.01.001","article-title":"Pathogen recognition and signalling in the Drosophila innate immune response","volume":"211","author":"L Wang","year":"2006","journal-title":"Immunobiology"},{"key":"ppat.1010826.ref037","doi-asserted-by":"crossref","first-page":"14614","DOI":"10.1073\/pnas.94.26.14614","article-title":"Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms","volume":"94","author":"B Lemaitre","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"ppat.1010826.ref038","doi-asserted-by":"crossref","first-page":"9465","DOI":"10.1073\/pnas.92.21.9465","article-title":"A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense","volume":"92","author":"B Lemaitre","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"ppat.1010826.ref039","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nature02021","article-title":"The immune response of Drosophila","volume":"426","author":"JA Hoffmann","year":"2003","journal-title":"Nature"},{"key":"ppat.1010826.ref040","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.it.2005.02.006","article-title":"Regulators of the Toll and Imd pathways in the Drosophila innate immune response","volume":"26","author":"T Tanji","year":"2005","journal-title":"Trends Immunol"},{"key":"ppat.1010826.ref041","doi-asserted-by":"crossref","first-page":"e2003026","DOI":"10.1371\/journal.pbio.2003026","article-title":"Ethoscopes: An open platform for high-throughput ethomics","volume":"15","author":"Q Geissmann","year":"2017","journal-title":"PLOS Biology"},{"key":"ppat.1010826.ref042","doi-asserted-by":"crossref","first-page":"e1001065","DOI":"10.1371\/journal.ppat.1001065","article-title":"Reciprocal Analysis of Francisella novicida Infections of a Drosophila melanogaster Model Reveal Host-Pathogen Conflicts Mediated by Reactive Oxygen and imd-Regulated Innate Immune Response","volume":"6","author":"MG Moule","year":"2010","journal-title":"PLOS Pathogens"},{"key":"ppat.1010826.ref043","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1111\/j.1462-5822.2008.01129.x","article-title":"Drosophila melanogaster as a model for elucidating the pathogenicity of Francisella tularensis","volume":"10","author":"M Vonkavaara","year":"2008","journal-title":"Cellular Microbiology"},{"key":"ppat.1010826.ref044","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.01419","article-title":"Origins of Metabolic Pathology in Francisella-Infected Drosophila","volume":"11","author":"CM Vincent","year":"2020","journal-title":"Front Immunol"},{"key":"ppat.1010826.ref045","doi-asserted-by":"crossref","first-page":"eaau9253","DOI":"10.1126\/sciadv.aau9253","article-title":"Most sleep does not serve a vital function: Evidence from Drosophila melanogaster","volume":"5","author":"Q Geissmann","year":"2019","journal-title":"Sci Adv"},{"key":"ppat.1010826.ref046","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1093\/emboj\/21.11.2568","article-title":"The Toll and Imd pathways are the major regulators of the immune response in Drosophila","volume":"21","author":"E De Gregorio","year":"2002","journal-title":"EMBO J"},{"key":"ppat.1010826.ref047","doi-asserted-by":"crossref","first-page":"e28298","DOI":"10.7554\/eLife.28298","article-title":"Stochastic variation in the initial phase of bacterial infection predicts the probability of survival in D. melanogaster","volume":"6","author":"D Duneau","year":"2017","journal-title":"eLife"},{"key":"ppat.1010826.ref048","doi-asserted-by":"crossref","first-page":"e44341","DOI":"10.7554\/eLife.44341","article-title":"Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach","volume":"8","author":"MA Hanson","year":"2019","journal-title":"eLife"},{"key":"ppat.1010826.ref049","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s12864-021-07593-3","article-title":"Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response","volume":"22","author":"F Schlamp","year":"2021","journal-title":"BMC Genomics"},{"key":"ppat.1010826.ref050","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1128\/IAI.71.7.4059-4066.2003","article-title":"The Drosophila melanogaster Toll pathway participates in resistance to infection by the Gram-Negative human pathogen Pseudomonas aeruginosa","volume":"71","author":"GW Lau","year":"2003","journal-title":"Infect Immun"},{"key":"ppat.1010826.ref051","doi-asserted-by":"crossref","first-page":"15119","DOI":"10.1073\/pnas.261573998","article-title":"A genome-wide analysis of immune responses in Drosophila","volume":"98","author":"P Irving","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010826.ref052","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.4049\/jimmunol.168.4.1542","article-title":"Cutting Edge: The Toll Pathway Is Required for Resistance to Gram-Positive Bacterial Infections in Drosophila","volume":"168","author":"S Rutschmann","year":"2002","journal-title":"The Journal of Immunology"},{"key":"ppat.1010826.ref053","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1242\/dmm.027102","article-title":"A novel mode of induction of the humoral innate immune response in Drosophila larvae","volume":"10","author":"H Kenmoku","year":"2017","journal-title":"Disease Models & Mechanisms"},{"key":"ppat.1010826.ref054","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1046\/j.1462-5822.2003.00329.x","article-title":"Exploration of host\u2013pathogen interactions using Listeria monocytogenes and Drosophila melanogaster","volume":"5","author":"BE Mansfield","year":"2003","journal-title":"Cellular Microbiology"},{"key":"ppat.1010826.ref055","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1128\/MMBR.65.2.232-260.2001","article-title":"Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance","volume":"65","author":"I Chopra","year":"2001","journal-title":"Microbiol Mol Biol Rev"},{"key":"ppat.1010826.ref056","doi-asserted-by":"crossref","first-page":"20853","DOI":"10.1073\/pnas.0906749106","article-title":"The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling","volume":"106","author":"JR DiAngelo","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010826.ref057","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/j.cub.2006.08.052","article-title":"Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila","volume":"16","author":"MS Dionne","year":"2006","journal-title":"Curr Biol"},{"key":"ppat.1010826.ref058","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.cell.2013.09.007","article-title":"MEF2 Is an In Vivo Immune-Metabolic Switch","volume":"155","author":"RI Clark","year":"2013","journal-title":"Cell"},{"key":"ppat.1010826.ref059","doi-asserted-by":"crossref","first-page":"e50679","DOI":"10.1371\/journal.pone.0050679","article-title":"Listeria monocytogenes infection causes metabolic shifts in Drosophila melanogaster","volume":"7","author":"MC Chambers","year":"2012","journal-title":"PLoS ONE"},{"key":"ppat.1010826.ref060","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/arch.20068","article-title":"Parasitic suppression of feeding in the tobacco hornworm, Manduca sexta: Parallels with feeding depression after an immune challenge","volume":"60","author":"SA Adamo","year":"2005","journal-title":"Archives of Insect Biochemistry and Physiology"},{"key":"ppat.1010826.ref061","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/S0899-9007(00)00421-4","article-title":"Anorexia of infection: current prospects","volume":"16","author":"W. Langhans","year":"2000","journal-title":"Nutrition"},{"key":"ppat.1010826.ref062","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.cub.2010.05.029","article-title":"Clock and cycle Limit Starvation-Induced Sleep Loss in Drosophila","volume":"20","author":"AC Keene","year":"2010","journal-title":"Current Biology"},{"key":"ppat.1010826.ref063","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1534\/genetics.167.1.311","article-title":"Hemolymph Sugar Homeostasis and Starvation-Induced Hyperactivity Affected by Genetic Manipulations of the Adipokinetic Hormone-Encoding Gene in Drosophila melanogaster","volume":"167","author":"G Lee","year":"2004","journal-title":"Genetics"},{"key":"ppat.1010826.ref064","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.1073\/pnas.1417838112","article-title":"Octopamine mediates starvation-induced hyperactivity in adult Drosophila","volume":"112","author":"Z Yang","year":"2015","journal-title":"PNAS"},{"key":"ppat.1010826.ref065","doi-asserted-by":"crossref","first-page":"e15693","DOI":"10.7554\/eLife.15693","article-title":"Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila","volume":"5","author":"Y Yu","year":"2016","journal-title":"eLife"},{"key":"ppat.1010826.ref066","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.devcel.2018.08.001","article-title":"Spatially restricted regulation of Sp\u00e4tzle\/Toll signaling during cell competition","volume":"46","author":"L Alpar","year":"2018","journal-title":"Dev Cell"},{"key":"ppat.1010826.ref067","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1742-4658.2009.07465.x","article-title":"Proteolytic activation and function of the cytokine Sp\u00e4tzle in innate immune response of a lepidopteran insect, Manduca sexta","volume":"277","author":"C An","year":"2010","journal-title":"FEBS J"},{"key":"ppat.1010826.ref068","doi-asserted-by":"crossref","first-page":"19502","DOI":"10.1074\/jbc.M109.098186","article-title":"Molecular mechanism that induces activation of Sp\u00e4tzle, the ligand for the Drosophila Toll receptor","volume":"285","author":"CJ Arnot","year":"2010","journal-title":"J Biol Chem"},{"key":"ppat.1010826.ref069","doi-asserted-by":"crossref","first-page":"649","DOI":"10.4049\/jimmunol.1002302","article-title":"The Drosophila Toll Signaling Pathway","volume":"186","author":"S Valanne","year":"2011","journal-title":"The Journal of Immunology"},{"key":"ppat.1010826.ref070","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/ni0202-121","article-title":"Drosophila innate immunity: an evolutionary perspective","volume":"3","author":"JA Hoffmann","year":"2002","journal-title":"Nat Immunol"},{"key":"ppat.1010826.ref071","doi-asserted-by":"crossref","first-page":"20160018","DOI":"10.1098\/rsbl.2016.0018","article-title":"Enhanced call effort in Japanese tree frogs infected by amphibian chytrid fungus","volume":"12","author":"D An","year":"2016","journal-title":"Biology Letters"},{"key":"ppat.1010826.ref072","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1016\/j.cub.2020.09.022","article-title":"Immune Receptor Signaling and the Mushroom Body Mediate Post-ingestion Pathogen Avoidance","volume":"30","author":"JM Kobler","year":"2020","journal-title":"Current Biology"},{"key":"ppat.1010826.ref073","doi-asserted-by":"crossref","first-page":"20140987","DOI":"10.1098\/rspb.2014.0987","article-title":"Sexual antagonism for resistance and tolerance to infection in Drosophila melanogaster","volume":"281","author":"CM Vincent","year":"2014","journal-title":"Proc R Soc B"},{"key":"ppat.1010826.ref074","doi-asserted-by":"crossref","DOI":"10.1186\/s13071-018-2805-9","article-title":"The missing link in parasite manipulation of host behaviour","volume":"11","author":"R Herbison","year":"2018","journal-title":"Parasit Vectors"},{"key":"ppat.1010826.ref075","doi-asserted-by":"crossref","first-page":"20131381","DOI":"10.1098\/rspb.2013.1381","article-title":"Behavioural fever is a synergic signal amplifying the innate immune response","volume":"280","author":"S Bolta\u00f1a","year":"2013","journal-title":"Proceedings of the Royal Society B: Biological Sciences"},{"key":"ppat.1010826.ref076","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1111\/1365-2435.13427","article-title":"Behavioural fever reduces ranaviral infection in toads","volume":"33","author":"EL Sauer","year":"2019","journal-title":"Functional Ecology"},{"key":"ppat.1010826.ref077","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1126\/science.aat4793","article-title":"Social network plasticity decreases disease transmission in a eusocial insect","volume":"362","author":"N Stroeymeyt","year":"2018","journal-title":"Science"},{"key":"ppat.1010826.ref078","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1016\/j.cub.2007.10.029","article-title":"Social Prophylaxis: Group Interaction Promotes Collective Immunity in Ant Colonies","volume":"17","author":"LV Ugelvig","year":"2007","journal-title":"Current Biology"},{"key":"ppat.1010826.ref079","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jinsphys.2016.08.005","article-title":"Cold temperature preference in bacterially infected Drosophila melanogaster improves survival but is remarkably suboptimal","volume":"93\u201394","author":"KM Fedorka","year":"2016","journal-title":"Journal of Insect Physiology"},{"key":"ppat.1010826.ref080","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1365-2656.2011.01901.x","article-title":"Behavioural resistance against a protozoan parasite in the monarch butterfly","volume":"81","author":"T Lef\u00e8vre","year":"2012","journal-title":"J Anim Ecol"},{"key":"ppat.1010826.ref081","doi-asserted-by":"crossref","first-page":"e2026554118","DOI":"10.1073\/pnas.2026554118","article-title":"Disparate regulation of IMD signaling drives sex differences in infection pathology in Drosophila melanogaster","volume":"118","author":"CM Vincent","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010826.ref082","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.iac.2009.02.002","article-title":"Cytokine, Sickness Behavior, and Depression","volume":"29","author":"R Dantzer","year":"2009","journal-title":"Immunol Allergy Clin North Am"},{"key":"ppat.1010826.ref083","doi-asserted-by":"crossref","first-page":"5415","DOI":"10.1113\/JP273009","article-title":"A mechanism for sickness sleep: lessons from invertebrates","volume":"595","author":"KC Davis","year":"2017","journal-title":"The Journal of Physiology"},{"key":"ppat.1010826.ref084","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.bbi.2019.10.020","article-title":"Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans","volume":"83","author":"J Lasselin","year":"2020","journal-title":"Brain, Behavior, and Immunity"},{"key":"ppat.1010826.ref085","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.cub.2020.10.012","article-title":"Astroglial Calcium Signaling Encodes Sleep Need in Drosophila","volume":"31","author":"ID Blum","year":"2021","journal-title":"Curr Biol"},{"key":"ppat.1010826.ref086","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1126\/science.aat1650","article-title":"A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila","volume":"363","author":"H Toda","year":"2019","journal-title":"Science"},{"key":"ppat.1010826.ref087","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1098\/rspb.2001.1641","article-title":"Parasitism and survival in a damselfly: does host sex matter?","volume":"268","author":"P Braune","year":"2001","journal-title":"Proc Biol Sci"},{"key":"ppat.1010826.ref088","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.4049\/jimmunol.1601896","article-title":"Sex-based differences in susceptibility to SARS-CoV infection","volume":"198","author":"R Channappanavar","year":"2017","journal-title":"J Immunol"},{"key":"ppat.1010826.ref089","doi-asserted-by":"crossref","first-page":"e1001271","DOI":"10.1371\/journal.pbio.1001271","article-title":"Host Sexual Dimorphism and Parasite Adaptation","volume":"10","author":"D Duneau","year":"2012","journal-title":"PLoS Biology"},{"key":"ppat.1010826.ref090","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12915-017-0466-3","article-title":"The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila","volume":"15","author":"DF Duneau","year":"2017","journal-title":"BMC Biol"},{"key":"ppat.1010826.ref091","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1098\/rstb.2008.0148","article-title":"On sexual dimorphism in immune function","volume":"364","author":"CL Nunn","year":"2009","journal-title":"Philosophical Transactions of the Royal Society B: Biological Sciences"},{"key":"ppat.1010826.ref092","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1098\/rspb.2002.1959","article-title":"Bateman\u2019s principle and immunity","volume":"269","author":"J. Rolff","year":"2002","journal-title":"Proceedings of the Royal Society B: Biological Sciences"},{"key":"ppat.1010826.ref093","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1111\/j.1420-9101.2011.02273.x","article-title":"Bateman\u2019s principle and immunity in a sex-role reversed pipefish","volume":"24","author":"O Roth","year":"2011","journal-title":"Journal of Evolutionary Biology"},{"key":"ppat.1010826.ref094","unstructured":"RStudio Team. RStudio: Integrated Development for R. RSudio, Inc. Boston, MA; 2015. http:\/\/www.rstudio.com\/"},{"key":"ppat.1010826.ref095","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.neuron.2009.07.021","article-title":"Obesity-blocking neurons in Drosophila","volume":"63","author":"B Al-Anzi","year":"2009","journal-title":"Neuron"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010826","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010826","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T13:59:53Z","timestamp":1664805593000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010826"}},"subtitle":[],"editor":[{"given":"Jacques","family":"Montagne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":95,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010826","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.24.457493","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]}}}