{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:41:02Z","timestamp":1784126462331,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009764","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2014-16\/529-2014-7552"],"award-info":[{"award-number":["2014-16\/529-2014-7552"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>The infection by <jats:italic>Trypanosoma brucei brucei<\/jats:italic> (<jats:italic>T<\/jats:italic>.<jats:italic>b<\/jats:italic>.<jats:italic>b<\/jats:italic>.), a protozoan parasite, is characterized by an early-systemic stage followed by a late stage in which parasites invade the brain parenchyma in a T cell-dependent manner.<\/jats:p>\n<jats:p>Here we found that early after infection effector-memory T cells were predominant among brain T cells, whereas, during the encephalitic stage T cells acquired a tissue resident memory phenotype (T<jats:sub>RM<\/jats:sub>) and expressed PD1. Both CD4 and CD8 T cells were independently redundant for the penetration of <jats:italic>T<\/jats:italic>.<jats:italic>b<\/jats:italic>.<jats:italic>b<\/jats:italic>. and other leukocytes into the brain parenchyma. The role of lymphoid cells during the <jats:italic>T<\/jats:italic>.<jats:italic>b<\/jats:italic>.<jats:italic>b<\/jats:italic>. infection was studied by comparing T- and B-cell deficient <jats:italic>rag1<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> and WT mice. Early after infection, parasites located in circumventricular organs, brain structures with increased vascular permeability, particularly in the median eminence (ME), paced closed to the sleep-wake regulatory arcuate nucleus of the hypothalamus (Arc). Whereas parasite levels in the ME were higher in <jats:italic>rag1<\/jats:italic><jats:sup>-\/-<\/jats:sup> than in WT mice, leukocytes were instead reduced. <jats:italic>Rag1<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> infected mice showed increased levels of <jats:italic>meca32<\/jats:italic> mRNA coding for a blood \/hypothalamus endothelial molecule absent in the blood-brain-barrier (BBB). Both immune and metabolic transcripts were elevated in the ME\/Arc of WT and <jats:italic>rag1<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice early after infection, except for <jats:italic>ifng<\/jats:italic> mRNA, which levels were only increased in WT mice. Finally, using a non-invasive sleep-wake cycle assessment method we proposed a putative role of lymphocytes in mediating sleep alterations during the infection with <jats:italic>T<\/jats:italic>.<jats:italic>b<\/jats:italic>.<jats:italic>b<\/jats:italic>.<\/jats:p>\n<jats:p>Thus, the majority of T cells in the brain during the early stage of <jats:italic>T<\/jats:italic>.<jats:italic>b<\/jats:italic>.<jats:italic>b<\/jats:italic>. infection expressed an effector-memory phenotype while T<jats:sub>RM<\/jats:sub> cells developed in the late stage of infection. T cells and parasites invade the ME\/Arc altering the metabolic and inflammatory responses during the early stage of infection and modulating sleep disturbances.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009764","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T19:41:22Z","timestamp":1632944482000},"page":"e0009764","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Role of T cells during the cerebral infection with Trypanosoma brucei"],"prefix":"10.1371","volume":"15","author":[{"given":"Gabriela C.","family":"Olivera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8856-3964","authenticated-orcid":true,"given":"Leonie","family":"Vetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9915-6424","authenticated-orcid":true,"given":"Chiara","family":"Tesoriero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0248-2456","authenticated-orcid":true,"given":"Federico","family":"Del Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustav","family":"Hedberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Basile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0514-7434","authenticated-orcid":true,"given":"Martin E.","family":"Rottenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"pntd.0009764.ref001","first-page":"215","volume-title":"Progress in human African trypanosomiasis, sleeping sickness","author":"Springer","year":"1999"},{"key":"pntd.0009764.ref002","first-page":"227","article-title":"Parasites and the brain: neuroinvasion, immunopathogenesis and neuronal dysfunctions","volume":"265","author":"K Kristensson","year":"2002","journal-title":"Curr Top Microbiol Immunol"},{"issue":"5","key":"pntd.0009764.ref003","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1172\/JCI22104","article-title":"Cerebral vessel laminins and IFN-gamma define Trypanosoma brucei brucei penetration of the blood-brain barrier","volume":"114","author":"W Masocha","year":"2004","journal-title":"J Clin Invest"},{"issue":"2","key":"pntd.0009764.ref004","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.pneurobio.2009.12.001","article-title":"African trypanosome infections of the nervous system: parasite entry and effects on sleep and synaptic functions","volume":"91","author":"K Kristensson","year":"2010","journal-title":"Prog Neurobiol"},{"issue":"2","key":"pntd.0009764.ref005","doi-asserted-by":"crossref","first-page":"e1005442","DOI":"10.1371\/journal.ppat.1005442","article-title":"Nitric Oxide Protects against Infection-Induced Neuroinflammation by Preserving the Stability of the Blood-Brain Barrier","volume":"12","author":"GC Olivera","year":"2016","journal-title":"PLoS Pathog"},{"issue":"10","key":"pntd.0009764.ref006","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1086\/644597","article-title":"Expression and role of CXCL10 during the encephalitic stage of experimental and clinical African trypanosomiasis","volume":"200","author":"DN Amin","year":"2009","journal-title":"J Infect Dis"},{"issue":"2","key":"pntd.0009764.ref007","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/infdis\/jir734","article-title":"Distinct Toll-like receptor signals regulate cerebral parasite load and interferon alpha\/beta and tumor necrosis factor alpha-dependent T-cell infiltration in the brains of Trypanosoma brucei-infected mice","volume":"205","author":"DN Amin","year":"2012","journal-title":"J Infect Dis"},{"issue":"8","key":"pntd.0009764.ref008","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1084\/jem.20151916","article-title":"Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection","volume":"213","author":"K Steinbach","year":"2016","journal-title":"J Exp Med"},{"issue":"9","key":"pntd.0009764.ref009","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.autrev.2018.03.014","article-title":"Pathogenic role of tissue-resident memory T cells in autoimmune diseases","volume":"17","author":"H Wu","year":"2018","journal-title":"Autoimmun Rev"},{"issue":"15","key":"pntd.0009764.ref010","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1002\/cne.23355","article-title":"Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain","volume":"521","author":"F Langlet","year":"2013","journal-title":"J Comp Neurol"},{"issue":"1","key":"pntd.0009764.ref011","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.brainresrev.2007.06.002","article-title":"The circumventricular organs: an atlas of comparative anatomy and vascularization","volume":"56","author":"HM Duvernoy","year":"2007","journal-title":"Brain Res Rev"},{"key":"pntd.0009764.ref012","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.2741\/3021","article-title":"Lymphocytic choriomeningitis infection of the central nervous system","volume":"13","author":"SS Kang","year":"2008","journal-title":"Front Biosci"},{"key":"pntd.0009764.ref013","doi-asserted-by":"crossref","first-page":"390","DOI":"10.3389\/fnins.2015.00390","article-title":"New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains","volume":"9","author":"S Miyata","year":"2015","journal-title":"Front Neurosci"},{"issue":"12","key":"pntd.0009764.ref014","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1128\/JVI.03219-15","article-title":"Entry Sites of Venezuelan and Western Equine Encephalitis Viruses in the Mouse Central Nervous System following Peripheral Infection","volume":"90","author":"AT Phillips","year":"2016","journal-title":"J Virol"},{"key":"pntd.0009764.ref015","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fncel.2015.00080","article-title":"The choroid plexus-a multi-role player during infectious diseases of the CNS","volume":"9","author":"C Schwerk","year":"2015","journal-title":"Front Cell Neurosci"},{"issue":"3","key":"pntd.0009764.ref016","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1365-2990.2008.00978.x","article-title":"Neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous route","volume":"35","author":"S Siso","year":"2009","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"6","key":"pntd.0009764.ref017","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s00401-010-0743-5","article-title":"Sensory circumventricular organs in health and disease","volume":"120","author":"S Siso","year":"2010","journal-title":"Acta Neuropathol"},{"key":"pntd.0009764.ref018","article-title":"Circumventricular Organs and Parasite Neurotropism: Neglected Gates to the Brain?","author":"M Bentivoglio","year":"2018","journal-title":"Frontiers in Immunology"},{"issue":"12","key":"pntd.0009764.ref019","doi-asserted-by":"crossref","first-page":"e0005242","DOI":"10.1371\/journal.pntd.0005242","article-title":"Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes","volume":"10","author":"C Laperchia","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pntd.0009764.ref020","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/jnr.490210109","article-title":"Spread of Trypanosoma brucei to the nervous system: early attack on circumventricular organs and sensory ganglia","volume":"21","author":"M Schultzberg","year":"1988","journal-title":"J Neurosci Res"},{"issue":"7388","key":"pntd.0009764.ref021","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nature10851","article-title":"Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity","volume":"483","author":"X Jiang","year":"2012","journal-title":"Nature"},{"issue":"7","key":"pntd.0009764.ref022","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/nm.3883","article-title":"The emerging role of resident memory T cells in protective immunity and inflammatory disease","volume":"21","author":"CO Park","year":"2015","journal-title":"Nat Med"},{"issue":"8","key":"pntd.0009764.ref023","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"EJ Wherry","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"pntd.0009764.ref024","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1038\/ncomms3049","article-title":"alpha-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors","volume":"4","author":"SC Robins","year":"2013","journal-title":"Nat Commun"},{"issue":"2","key":"pntd.0009764.ref025","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.neulet.2010.10.019","article-title":"The arcuate nucleus as a circumventricular organ in the mouse","volume":"487","author":"P Ciofi","year":"2011","journal-title":"Neurosci Lett"},{"issue":"4","key":"pntd.0009764.ref026","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.cmet.2013.03.004","article-title":"Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting","volume":"17","author":"F Langlet","year":"2013","journal-title":"Cell Metab"},{"issue":"51","key":"pntd.0009764.ref027","doi-asserted-by":"crossref","first-page":"32529","DOI":"10.1074\/jbc.271.51.32529","article-title":"Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1","volume":"271","author":"GL Semenza","year":"1996","journal-title":"J Biol Chem"},{"issue":"38","key":"pntd.0009764.ref028","doi-asserted-by":"crossref","first-page":"23757","DOI":"10.1016\/S0021-9258(17)31580-6","article-title":"Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1","volume":"269","author":"GL Semenza","year":"1994","journal-title":"J Biol Chem"},{"issue":"6398","key":"pntd.0009764.ref029","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/359843a0","article-title":"Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis","volume":"359","author":"D Shweiki","year":"1992","journal-title":"Nature"},{"issue":"1","key":"pntd.0009764.ref030","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cmet.2014.12.005","article-title":"Pyruvate kinase M2 regulates Hif-1alpha activity and IL-1beta induction and is a critical determinant of the warburg effect in LPS-activated macrophages","volume":"21","author":"EM Palsson-McDermott","year":"2015","journal-title":"Cell Metab"},{"issue":"7444","key":"pntd.0009764.ref031","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha","volume":"496","author":"GM Tannahill","year":"2013","journal-title":"Nature"},{"issue":"2","key":"pntd.0009764.ref032","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbi.2004.06.001","article-title":"IL-1 type I receptor plays a key role in mediating the recruitment of leukocytes into the central nervous system","volume":"19","author":"S Ching","year":"2005","journal-title":"Brain Behav Immun"},{"key":"pntd.0009764.ref033","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.brainresbull.2018.07.002","article-title":"Sleep and brain infections","volume":"145","author":"C Tesoriero","year":"2019","journal-title":"Brain Res Bull"},{"issue":"2","key":"pntd.0009764.ref034","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0361-9230(94)00265-3","article-title":"Sleep fragmentation, and changes in locomotor activity and body temperature in trypanosome-infected rats","volume":"37","author":"G Grassi-Zucconi","year":"1995","journal-title":"Brain Res Bull"},{"issue":"36","key":"pntd.0009764.ref035","doi-asserted-by":"crossref","first-page":"14288","DOI":"10.1523\/JNEUROSCI.5102-12.2013","article-title":"Effects of sleep and wake on oligodendrocytes and their precursors","volume":"33","author":"M Bellesi","year":"2013","journal-title":"J Neurosci"},{"issue":"11","key":"pntd.0009764.ref036","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1038\/nn.2934","article-title":"Sleep and waking modulate spine turnover in the adolescent mouse cortex","volume":"14","author":"S Maret","year":"2011","journal-title":"Nat Neurosci"},{"key":"pntd.0009764.ref037","first-page":"e13187","article-title":"Sleep inhibition induced by amyloid-beta oligomers is mediated by the cellular prion protein","author":"F Del Gallo","year":"2020","journal-title":"J Sleep Res"},{"issue":"12","key":"pntd.0009764.ref038","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1038\/ni.2744","article-title":"The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin","volume":"14","author":"LK Mackay","year":"2013","journal-title":"Nat Immunol"},{"issue":"6","key":"pntd.0009764.ref039","doi-asserted-by":"crossref","first-page":"983","DOI":"10.4269\/ajtmh.2010.09-0770","article-title":"Identification of stage biomarkers for human African trypanosomiasis","volume":"82","author":"DN Amin","year":"2010","journal-title":"The American journal of tropical medicine and hygiene"},{"issue":"12","key":"pntd.0009764.ref040","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1523\/JNEUROSCI.0037-09.2009","article-title":"E-Cadherin regulates neural stem cell self-renewal","volume":"29","author":"P Karpowicz","year":"2009","journal-title":"J Neurosci"},{"issue":"42","key":"pntd.0009764.ref041","doi-asserted-by":"crossref","first-page":"17872","DOI":"10.1073\/pnas.1010201107","article-title":"Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence","volume":"107","author":"LM Wakim","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"pntd.0009764.ref042","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.4049\/jimmunol.1400003","article-title":"Cutting edge: resident memory CD8 T cells occupy frontline niches in secondary lymphoid organs","volume":"192","author":"JM Schenkel","year":"2014","journal-title":"J Immunol"},{"issue":"4","key":"pntd.0009764.ref043","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/ni.3108","article-title":"Proinflammatory microenvironments within the intestine regulate the differentiation of tissue-resident CD8(+) T cells responding to infection","volume":"16","author":"T Bergsbaken","year":"2015","journal-title":"Nat Immunol"},{"issue":"4","key":"pntd.0009764.ref044","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.cell.2015.03.031","article-title":"Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance","volume":"161","author":"EM Steinert","year":"2015","journal-title":"Cell"},{"issue":"45","key":"pntd.0009764.ref045","doi-asserted-by":"crossref","first-page":"19408","DOI":"10.1073\/pnas.1006298107","article-title":"Distinct functions of antigen-specific CD4 T cells during murine Mycobacterium tuberculosis infection","volume":"107","author":"WW Reiley","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pntd.0009764.ref046","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nprot.2014.005","article-title":"Intravascular staining for discrimination of vascular and tissue leukocytes","volume":"9","author":"KG Anderson","year":"2014","journal-title":"Nat Protoc"},{"issue":"9","key":"pntd.0009764.ref047","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1002\/eji.1830240942","article-title":"Class II major histocompatibility complex-restricted T cell function in CD4-deficient mice","volume":"24","author":"A Rahemtulla","year":"1994","journal-title":"Eur J Immunol"},{"issue":"4","key":"pntd.0009764.ref048","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1084\/jem.20031961","article-title":"The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells","volume":"199","author":"AJ Tyznik","year":"2004","journal-title":"J Exp Med"},{"issue":"6340","key":"pntd.0009764.ref049","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/353180a0","article-title":"Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4","volume":"353","author":"A Rahemtulla","year":"1991","journal-title":"Nature"},{"issue":"5617","key":"pntd.0009764.ref050","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1126\/science.1083317","article-title":"Defective CD8 T cell memory following acute infection without CD4 T cell help","volume":"300","author":"JC Sun","year":"2003","journal-title":"Science"},{"issue":"1","key":"pntd.0009764.ref051","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1128\/IAI.70.1.185-191.2002","article-title":"Deficient humoral responses underlie susceptibility to Toxoplasma gondii in CD4-deficient mice","volume":"70","author":"LL Johnson","year":"2002","journal-title":"Infect Immun"},{"issue":"1\u20132","key":"pntd.0009764.ref052","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0165-2478(94)00221-C","article-title":"Outcome of infection with different strains of Trypanosoma cruzi in mice lacking CD4 and\/or CD8","volume":"45","author":"ME Rottenberg","year":"1995","journal-title":"Immunol Lett"},{"issue":"2","key":"pntd.0009764.ref053","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuron.2020.04.020","article-title":"MCH Neurons Regulate Permeability of the Median Eminence Barrier","volume":"107","author":"H Jiang","year":"2020","journal-title":"Neuron"},{"issue":"8","key":"pntd.0009764.ref054","doi-asserted-by":"crossref","first-page":"e0005854","DOI":"10.1371\/journal.pntd.0005854","article-title":"Expression of interferon-inducible chemokines and sleep\/wake changes during early encephalitis in experimental African trypanosomiasis","volume":"11","author":"C Laperchia","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0009764.ref055","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1093\/sleep\/31.3.348","article-title":"Hypocretin and human African trypanosomiasis","volume":"31","author":"Y Dauvilliers","year":"2008","journal-title":"Sleep"},{"key":"pntd.0009764.ref056","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fnana.2018.00013","article-title":"Neural Damage in Experimental Trypanosoma brucei gambiense Infection: Hypothalamic Peptidergic Sleep and Wake-Regulatory Neurons","volume":"12","author":"C Laperchia","year":"2018","journal-title":"Front Neuroanat"},{"key":"pntd.0009764.ref057","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.neuroscience.2014.12.066","article-title":"Alterations of orexinergic and melanin-concentrating hormone neurons in experimental sleeping sickness","volume":"290","author":"M Palomba","year":"2015","journal-title":"Neuroscience"},{"key":"pntd.0009764.ref058","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaut.2019.03.010","article-title":"Shared T cell receptor chains in blood memory CD4(+) T cells of narcolepsy type 1 patients","volume":"100","author":"E Beltran","year":"2019","journal-title":"J Autoimmun"},{"issue":"7725","key":"pntd.0009764.ref059","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41586-018-0540-1","article-title":"T cells in patients with narcolepsy target self-antigens of hypocretin neurons","volume":"562","author":"D Latorre","year":"2018","journal-title":"Nature"},{"issue":"3","key":"pntd.0009764.ref060","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1474-4422(14)70218-2","article-title":"Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy","volume":"14","author":"RS Liblau","year":"2015","journal-title":"Lancet Neurol"},{"issue":"1","key":"pntd.0009764.ref061","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/s41467-019-08774-1","article-title":"CD8(+) T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens","volume":"10","author":"NW Pedersen","year":"2019","journal-title":"Nat Commun"},{"issue":"30","key":"pntd.0009764.ref062","doi-asserted-by":"crossref","first-page":"26873","DOI":"10.1074\/jbc.M111.238287","article-title":"Silencing Suppressor of Cytokine Signaling-1 in Macrophages Improves Mycobacterium tuberculosis Control in an Interferon-g (IFN-g)-dependent Manner","volume":"286","author":"B Carow","year":"2011","journal-title":"The Journal of biological chemistry"},{"issue":"1","key":"pntd.0009764.ref063","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1177\/0748730411431550","article-title":"Rapid assessment of sleep-wake behavior in mice","volume":"27","author":"SP Fisher","year":"2012","journal-title":"J Biol Rhythms"},{"issue":"2","key":"pntd.0009764.ref064","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1152\/physiolgenomics.00139.2006","article-title":"Novel method for high-throughput phenotyping of sleep in mice","volume":"28","author":"AI Pack","year":"2007","journal-title":"Physiol Genomics"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0009764","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T18:29:28Z","timestamp":1634840968000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009764"}},"subtitle":[],"editor":[{"given":"Mary Ann","family":"McDowell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":64,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0009764","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0009764","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]}}}