{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:45:02Z","timestamp":1775976302125,"version":"3.50.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM113123-01"],"award-info":[{"award-number":["P20GM113123-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"DOI":"10.3389\/fmicb.2018.00811","type":"journal-article","created":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T04:17:07Z","timestamp":1524629827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Primary Human Microglia Are Phagocytically Active and Respond to Borrelia burgdorferi With Upregulation of Chemokines and Cytokines"],"prefix":"10.3389","volume":"9","author":[{"given":"Jacob R.","family":"Greenmyer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Gaultney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine A.","family":"Brissette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Watt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2018,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1128\/JB.186.9.2745-2756.2004","article-title":"Molecular characterization of Borrelia burgdorferi erp promoter\/operator elements.","volume":"186","author":"Babb","year":"2004","journal-title":"J. Bacteriol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1007\/s00415-013-6831-4","article-title":"Neuroborreliosis-associated cerebral vasculitis: long-term outcome and health-related quality of life.","volume":"260","author":"Back","year":"2013","journal-title":"J. Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"4385","DOI":"10.1128\/IAI.00394-08","article-title":"Toll-like receptors: insights into their possible role in the pathogenesis of Lyme neuroborreliosis.","volume":"76","author":"Bernardino","year":"2008","journal-title":"Infect. Immun."},{"key":"B4","first-page":"43","article-title":"Central nervous system infection caused by Borrelia burgdorferi. Clinico-pathological correlation of three post-mortem cases.","volume":"37","author":"Bertrand","year":"1999","journal-title":"Folia Neuropathol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4103\/2152-7806.118349","article-title":"Immunology primer for neurosurgeons and neurologists part 2: innate brain immunity.","volume":"4","author":"Blaylock","year":"2013","journal-title":"Surg. Neurol. Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2652","DOI":"10.1172\/JCI58813","article-title":"Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy.","volume":"122","author":"Bockenstedt","year":"2012","journal-title":"J. Clin. Invest."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-1012-5","article-title":"Human microglia and astrocytes constitutively express the neurokinin-1 receptor and functionally respond to substance P.","volume":"14","author":"Burmeister","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1046\/j.1365-2958.2000.01698.x","article-title":"A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs of an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi.","volume":"35","author":"Casjens","year":"2000","journal-title":"Mol. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1097\/00005072-200606000-00002","article-title":"Borrelia burgdorferi Induces TLR1 and TLR2 in human microglia and peripheral blood monocytes but differentially regulates HLA-class II expression.","volume":"65","author":"Cassiani-Ingoni","year":"2006","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00055","article-title":"Phagosomal TLR signaling upon Borrelia burgdorferi infection.","volume":"4","author":"Cervantes","year":"2014","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"8241","DOI":"10.4049\/jimmunol.180.12.8241","article-title":"Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi.","volume":"180","author":"Chauhan","year":"2008","journal-title":"J. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.ajpath.2017.11.005","article-title":"Late disseminated Lyme disease: associated pathology and spirochete persistence post-treatment in rhesus macaques.","volume":"188","author":"Crossland","year":"2017","journal-title":"Am. J. Pathol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029914","article-title":"Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection.","volume":"7","author":"Embers","year":"2012","journal-title":"PLoS One"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189071","article-title":"Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding.","volume":"12","author":"Embers","year":"2017","journal-title":"PLoS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1212\/01.WNL.0000284604.61160.2d","article-title":"A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.","volume":"70","author":"Fallon","year":"2008","journal-title":"Neurology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.nbd.2009.11.016","article-title":"Inflammation and central nervous system Lyme disease.","volume":"37","author":"Fallon","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1176\/ajp.151.11.1571","article-title":"Lyme disease: a neuropsychiatric illness.","volume":"151","author":"Fallon","year":"1994","journal-title":"Am. J. Psychiatry"},{"key":"B18","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1038\/37551","article-title":"Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi.","volume":"390","author":"Fraser","year":"1997","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1089\/neu.2015.4234","article-title":"Leukemia inhibitory factor haplodeficiency desynchronizes glial reactivity and exacerbates damage and functional deficits after a concussive brain injury.","volume":"33","author":"Goodus","year":"2016","journal-title":"J. Neurotrauma"},{"key":"B20","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/nn.4189","article-title":"Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain.","volume":"19","author":"Guan","year":"2016","journal-title":"Nat. Neurosci."},{"key":"B21","first-page":"91","article-title":"Neurological and psychological symptoms after the severe acute neuroborreliosis.","volume":"8","author":"Gustaw","year":"2001","journal-title":"Ann. Agric. Environ. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.cll.2015.07.002","article-title":"Nervous system Lyme disease.","volume":"35","author":"Halperin","year":"2015","journal-title":"Clin. Lab. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1073\/pnas.1112078109","article-title":"CD14 cooperates with complement receptor 3 to mediate MyD88-independent phagocytosis of Borrelia burgdorferi.","volume":"109","author":"Hawley","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.7326\/0003-4819-157-3-201208070-01002","article-title":"In the clinic. Lyme disease.","volume":"157","author":"Hu","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1126\/science.aaf8924","article-title":"Pain regulation by non-neuronal cells and inflammation.","volume":"354","author":"Ji","year":"2016","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00296","article-title":"The therapeutic potential of targeting substance P\/NK-1R interactions in inflammatory CNS disorders.","volume":"10","author":"Johnson","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.jneuroim.2005.06.030","article-title":"Murine microglia are effective phagocytes for Borrelia burgdorferi.","volume":"168","author":"Kuhlow","year":"2005","journal-title":"J. Neurimmunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"33","DOI":"10.2174\/1389203711314010006","article-title":"Toll-like receptors: sensor molecules for detecting damage to the nervous system.","volume":"14","author":"Lee","year":"2013","journal-title":"Curr. Protein Pept. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1111\/j.1468-1331.2009.02756.x","article-title":"Remaining complaints 1 year after treatment for acute Lyme neuroborreliosis; frequency, pattern and risk factors.","volume":"17","author":"Ljostad","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1093\/brain\/awu377","article-title":"Evidence for brain glial activation in chronic pain patients.","author":"Loggia","year":"2015","journal-title":"Brain"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0813-x","article-title":"Aprepitant limits in vivo neuroinflammatory responses in a rhesus model of Lyme neuroborreliosis.","volume":"14","author":"Martinez","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"B32","doi-asserted-by":"publisher","first-page":"6943","DOI":"10.1128\/IAI.71.12.6943-6952.2003","article-title":"Temporal analysis of Borrelia burgdorferi Erp protein expression throughout the mammal-tick infectious cycle.","volume":"71","author":"Miller","year":"2003","journal-title":"Infect. Immun."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000659","article-title":"Microglia are mediators of Borrelia burgdorferi-induced apoptosis in SH-SY5Y neuronal cells.","volume":"5","author":"Myers","year":"2009","journal-title":"PLoS Pathog."},{"key":"B34","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/j.1468-1331.2009.02862.x","article-title":"EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis.","author":"Mygland","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/S0046-8177(96)90279-8","article-title":"Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: possible factors contributing to persistence of organisms.","volume":"27","author":"Nanagara","year":"1996","journal-title":"Hum. Pathol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.neulet.2013.10.032","article-title":"Non-viable Borrelia burgdorferi induce inflammatory mediators and apoptosis in human oligodendrocytes.","volume":"556","author":"Parthasarathy","year":"2013","journal-title":"Neurosci. Lett."},{"key":"B37","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1007\/s10495-013-0913-8","article-title":"The MEK\/ERK pathway is the primary conduit for Borrelia burgdorferi-induced inflammation and P53-mediated apoptosis in oligodendrocytes.","volume":"19","author":"Parthasarathy","year":"2013","journal-title":"Apoptosis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0274-z","article-title":"Inflammatory mediator release from primary rhesus microglia in response to Borrelia burgdorferi results from the activation of several receptors and pathways.","volume":"12","author":"Parthasarathy","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"B39","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1128\/IAI.00890-12","article-title":"TRIF mediates toll-like receptor 2-dependent inflammatory responses to Borrelia burgdorferi.","volume":"81","author":"Petnicki-Ocwieja","year":"2013","journal-title":"Infect. Immun."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-6-23","article-title":"Possible role of glial cells in the onset and progression of Lyme neuroborreliosis.","volume":"6","author":"Ramesh","year":"2009","journal-title":"J. Neuroinflammation"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.ajpath.2015.01.024","article-title":"Inflammation in the pathogenesis of Lyme neuroborreliosis.","volume":"185","author":"Ramesh","year":"2015","journal-title":"Am. J. Pathol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-88","article-title":"The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia.","volume":"10","author":"Ramesh","year":"2013","journal-title":"J. Neuroinflammation"},{"key":"B43","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0165-5728(02)00187-X","article-title":"Borrelia burgdorferi induces inflammatory mediator production by murine microglia.","volume":"130","author":"Rasley","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"B44","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2119\/2007-00091.Rupprecht","article-title":"The pathogenesis of lyme neuroborreliosis: from infection to inflammation.","volume":"14","author":"Rupprecht","year":"2008","journal-title":"Mol. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method.","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"B46","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1002\/art.1780310405","article-title":"Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue.","volume":"31","author":"Steere","year":"1988","journal-title":"Arthritis Rheum."},{"key":"B47","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jneuroim.2006.06.009","article-title":"Characterization of nucleotide-binding oligomerization domain (NOD) protein expression in primary murine microglia.","volume":"179","author":"Sterka","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1002\/glia.20286","article-title":"Functional expression of NOD2, a novel pattern recognition receptor for bacterial motifs, in primary murine astrocytes.","volume":"53","author":"Sterka","year":"2006","journal-title":"Glia"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1128\/IAI.03097-14","article-title":"Motor rotation is essential for the formation of the periplasmic flagellar ribbon, cellular morphology, and Borrelia burgdorferi persistence within Ixodes scapularis tick and murine hosts.","volume":"83","author":"Sultan","year":"2015","journal-title":"Infect. Immun."},{"key":"B50","first-page":"1120","article-title":"Brain perfusion SPECT in Lyme neuroborreliosis.","volume":"38","author":"Sumiya","year":"1997","journal-title":"J. Nucl. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/jcbfm.2008.141","article-title":"Ambivalent aspects of interleukin-6 in cerebral ischemia: inflammatory versus neurotrophic aspects.","volume":"29","author":"Suzuki","year":"2009","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B52","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1097\/NEN.0b013e3182289acd","article-title":"Long-term intrathecal infusion of outer surface protein C from Borrelia burgdorferi causes axonal damage.","volume":"70","author":"Tauber","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.ijantimicag.2012.11.016","article-title":"In vitro susceptibility of European human Borrelia burgdorferi sensu stricto strains to antimicrobial agents.","volume":"41","author":"Veinovic","year":"2013","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B54","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1007\/s10067-012-1964-x","article-title":"The amber theory of Lyme arthritis: initial description and clinical implications.","volume":"31","author":"Wormser","year":"2012","journal-title":"Clin. Rheumatol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s10571-014-0101-6","article-title":"Microglial Abeta receptors in Alzheimer\u2019s disease.","volume":"35","author":"Yu","year":"2015","journal-title":"Cell. Mol. Neurobiol."},{"key":"B56","first-page":"11","article-title":"Laboratory maintenance of Borrelia burgdorferi. Current protocols","author":"Z\u00fcckert","year":"2007","journal-title":"Microbiology"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fmicb.2018.00811\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T01:04:52Z","timestamp":1571274292000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fmicb.2018.00811\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,25]]},"references-count":56,"alternative-id":["10.3389\/fmicb.2018.00811"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2018.00811","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,25]]},"article-number":"811"}}