{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:07:38Z","timestamp":1788520058250,"version":"build-2803163510"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T00:00:00Z","timestamp":1525651200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI058086, AI119821"],"award-info":[{"award-number":["AI058086, AI119821"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2018.00959","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T04:16:13Z","timestamp":1525666573000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["The Classical Complement Pathway Is Required to Control Borrelia burgdorferi Levels During Experimental Infection"],"prefix":"10.3389","volume":"9","author":[{"given":"Hui","family":"Zhi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon T.","family":"Skare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,5,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1093\/cid\/ciu397","article-title":"Lyme disease testing by large commercial laboratories in the United States","volume":"59","author":"Hinckley","year":"2014","journal-title":"Clin Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1749-6632.1988.tb31839.x","article-title":"Clinical pathologic correlations of Lyme disease by stage","volume":"539","author":"Duray","year":"1988","journal-title":"Ann N Y Acad Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1056\/NEJMcp1314325","article-title":"Lyme disease","volume":"370","author":"Shapiro","year":"2014","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1056\/NEJM200107123450207","article-title":"Lyme disease","volume":"345","author":"Steere","year":"2001","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1172\/JCI21681","article-title":"The emergence of Lyme disease","volume":"113","author":"Steere","year":"2004","journal-title":"J Clin Invest"},{"key":"B6","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1038\/ni1113","article-title":"The complement system in regulation of adaptive immunity","volume":"5","author":"Carroll","year":"2004","journal-title":"Nat Immunol"},{"key":"B7","first-page":"43","article-title":"The complement system and innate immunity","volume-title":"Immunobiology: The Immune System in Health and Disease","author":"Charles","year":"2001"},{"key":"B8","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/cr.2009.139","article-title":"Complement and its role in innate and adaptive immune responses","volume":"20","author":"Dunkelberger","year":"2010","journal-title":"Cell Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nri1994","article-title":"T-cell regulation: with complements from innate immunity","volume":"7","author":"Kemper","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1016\/j.molimm.2007.11.003","article-title":"The tick-over theory revisited: formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb)","volume":"45","author":"Bexborn","year":"2008","journal-title":"Mol Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/j.1749-6632.1983.tb18116.x","article-title":"Initiation of the alternative complement pathway due to spontaneous hydrolysis of the thioester of C3","volume":"421","author":"Pangburn","year":"1983","journal-title":"Ann N Y Acad Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.4049\/jimmunol.1600863","article-title":"Novel evasion mechanisms of the classical complement pathway","volume":"197","author":"Garcia","year":"2016","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imbio.2009.08.006","article-title":"Paths reunited: initiation of the classical and lectin pathways of complement activation","volume":"215","author":"Wallis","year":"2010","journal-title":"Immunobiology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.molimm.2017.05.025","article-title":"C1q: a fresh look upon an old molecule","volume":"89","author":"Thielens","year":"2017","journal-title":"Mol Immunol"},{"key":"B15","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.4049\/jimmunol.138.4.1150","article-title":"Modulation of FcR function by complement: subcomponent C1q enhances the phagocytosis of IgG-opsonized targets by human monocytes and culture-derived macrophages","volume":"138","author":"Bobak","year":"1987","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3389\/fimmu.2014.00402","article-title":"Complement, c1q, and c1q-related molecules regulate macrophage polarization","volume":"5","author":"Bohlson","year":"2014","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"5682","DOI":"10.4049\/jimmunol.1103760","article-title":"Complement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells","volume":"188","author":"Benoit","year":"2012","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1189\/jlb.3MR0214-109R","article-title":"Complement modulation of T cell immune responses during homeostasis and disease","volume":"96","author":"Clarke","year":"2014","journal-title":"J Leukoc Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"5612","DOI":"10.4049\/jimmunol.1103735","article-title":"Delays and diversions mark the development of B cell responses to Borrelia burgdorferi infection","volume":"188","author":"Hastey","year":"2012","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e1004976","DOI":"10.1371\/journal.ppat.1004976","article-title":"Suppression of long-lived humoral immunity following Borrelia burgdorferi infection","volume":"11","author":"Elsner","year":"2015","journal-title":"PLoS Pathog"},{"key":"B21","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1128\/IAI.65.4.1228-1236.1997","article-title":"Complement-mediated serum sensitivity among spirochetes that cause Lyme disease","volume":"65","author":"van Dam","year":"1997","journal-title":"Infect Immun"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e12786","DOI":"10.1111\/cmi.12786","article-title":"Borrelia burgdorferi outer surface protein C (OspC) binds complement component C4b and confers bloodstream survival","volume":"19","author":"Caine","year":"2017","journal-title":"Cell Microbiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e1005404","DOI":"10.1371\/journal.ppat.1005404","article-title":"Borrelia burgdorferi BBK32 inhibits the classical pathway by blocking activation of the C1 complement complex","volume":"12","author":"Garcia","year":"2016","journal-title":"PLoS Pathog"},{"key":"B24","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1128\/IAI.69.1.446-455.2001","article-title":"Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28-1","volume":"69","author":"Labandeira-Rey","year":"2001","journal-title":"Infect Immun"},{"key":"B25","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1111\/j.1365-2958.2011.07801.x","article-title":"Bioluminescent imaging of Borrelia burgdorferi in vivo demonstrates that the fibronectin-binding protein BBK32 is required for optimal infectivity","volume":"82","author":"Hyde","year":"2011","journal-title":"Mol Microbiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1159\/000019076","article-title":"C1q knock-out mice for the study of complement deficiency in autoimmune disease","volume":"15","author":"Botto","year":"1998","journal-title":"Exp Clin Immunogenet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1111\/j.1365-2958.2009.06951.x","article-title":"The BosR regulatory protein of Borrelia burgdorferi interfaces with the RpoS regulatory pathway and modulates both the oxidative stress response and pathogenic properties of the Lyme disease spirochete","volume":"74","author":"Hyde","year":"2009","journal-title":"Mol Microbiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5694","DOI":"10.1128\/IAI.00690-08","article-title":"Borrelia burgdorferi lacking DbpBA exhibits an early survival defect during experimental infection","volume":"76","author":"Weening","year":"2008","journal-title":"Infect Immun"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1128\/JCM.40.4.1249-1253.2002","article-title":"Quantitative detection of Borrelia burgdorferi in 2-millimeter skin samples of erythema migrans lesions: correlation of results with clinical and laboratory findings","volume":"40","author":"Liveris","year":"2002","journal-title":"J Clin Microbiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1084\/jem.20070962","article-title":"Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis","volume":"205","author":"Pal","year":"2008","journal-title":"J Exp Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1086\/340826","article-title":"Human phagocytic cells in the early innate immune response to Borrelia burgdorferi","volume":"185","author":"Montgomery","year":"2002","journal-title":"J Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s12026-015-8705-6","article-title":"Fundamental role of C1q in autoimmunity and inflammation","volume":"63","author":"Son","year":"2015","journal-title":"Immunol Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3389\/fimmu.2015.00317","article-title":"Emerging and novel functions of complement protein C1q","volume":"6","author":"Kouser","year":"2015","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1128\/IAI.61.11.4696-4702.1993","article-title":"Passive immunizing activity of sera from mice infected with Borrelia burgdorferi","volume":"61","author":"Barthold","year":"1993","journal-title":"Infect Immun"},{"key":"B35","first-page":"57","article-title":"Serum-mediated resolution of Lyme arthritis in mice","volume":"74","author":"Barthold","year":"1996","journal-title":"Lab Invest"},{"key":"B36","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1086\/516166","article-title":"Protective and arthritis-resolving activity in sera of mice infected with Borrelia burgdorferi","volume":"25","author":"Barthold","year":"1997","journal-title":"Clin Infect Dis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1128\/IAI.71.5.2938-2940.2003","article-title":"Humoral immunity reflects altered T helper cell bias in Borrelia burgdorferi-infected gamma delta T-cell-deficient mice","volume":"71","author":"Bockenstedt","year":"2003","journal-title":"Infect Immun"},{"key":"B38","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1093\/infdis\/169.3.568","article-title":"Sera from patients with chronic Lyme disease protect mice from Lyme borreliosis","volume":"169","author":"Fikrig","year":"1994","journal-title":"J Infect Dis"},{"key":"B39","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1128\/IAI.56.2.314-321.1988","article-title":"Role of immunoglobulin G in killing of Borrelia burgdorferi by the classical complement pathway","volume":"56","author":"Kochi","year":"1988","journal-title":"Infect Immun"},{"key":"B40","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s004300050038","article-title":"Heterogeneity in the complement-dependent bacteriolysis within the species of Borrelia burgdorferi","volume":"185","author":"Breitner-Ruddock","year":"1997","journal-title":"Med Microbiol Immunol"},{"key":"B41","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1128\/IAI.59.10.3815-3818.1991","article-title":"Depletion of complement and effects on passive transfer of resistance to infection with Borrelia burgdorferi","volume":"59","author":"Schmitz","year":"1991","journal-title":"Infect Immun"},{"key":"B42","doi-asserted-by":"publisher","first-page":"10752","DOI":"10.1073\/pnas.0901858106","article-title":"The bactericidal effect of a complement-independent antibody is osmolytic and specific to Borrelia","volume":"106","author":"LaRocca","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.4049\/jimmunol.164.3.1425","article-title":"A bactericidal monoclonal antibody elicits a change in its antigen, OspB of Borrelia burgdorferi, that can be detected by limited proteolysis","volume":"164","author":"Katona","year":"2000","journal-title":"J Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/S0167-5699(00)01754-0","article-title":"Natural antibodies and complement link innate and acquired immunity","volume":"21","author":"Ochsenbein","year":"2000","journal-title":"Immunol Today"},{"key":"B45","doi-asserted-by":"publisher","first-page":"6456","DOI":"10.1128\/IAI.69.10.6456-6462.2001","article-title":"Natural antibody affects survival of the spirochete Borrelia burgdorferi within feeding ticks","volume":"69","author":"Belperron","year":"2001","journal-title":"Infect Immun"},{"key":"B46","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3389\/fimmu.2016.00385","article-title":"Hide and seek: how Lyme disease spirochetes overcome complement attack","volume":"7","author":"Kraiczy","year":"2016","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3389\/fimmu.2017.00116","article-title":"Borrelia burgdorferi manipulates innate and adaptive immunity to establish persistence in rodent reservoir hosts","volume":"8","author":"Tracy","year":"2017","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"6096","DOI":"10.4049\/jimmunol.164.12.6096","article-title":"Cutting edge: T cell-mediated pathology in murine Lyme borreliosis","volume":"164","author":"McKisic","year":"2000","journal-title":"J Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"647","DOI":"10.3389\/fimmu.2016.00647","article-title":"C1q deficiency and neuropsychiatric systemic lupus erythematosus","volume":"7","author":"van Schaarenburg","year":"2016","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.cyto.2014.12.027","article-title":"Th1\/Th2\/Th17\/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: correlation with disease activity","volume":"72","author":"Talaat","year":"2015","journal-title":"Cytokine"},{"key":"B51","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1191\/096120300678828703","article-title":"Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus","volume":"9","author":"Wong","year":"2000","journal-title":"Lupus"},{"key":"B52","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1189\/jlb.3A0614-278R","article-title":"Complement protein C1q bound to apoptotic cells suppresses human macrophage and dendritic cell-mediated Th17 and Th1 T cell subset proliferation","volume":"97","author":"Clarke","year":"2015","journal-title":"J Leukoc Biol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"865","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":"B54","doi-asserted-by":"publisher","first-page":"7076","DOI":"10.4049\/jimmunol.177.10.7076","article-title":"IL-10 deficiency promotes increased Borrelia burgdorferi clearance predominantly through enhanced innate immune responses","volume":"177","author":"Lazarus","year":"2006","journal-title":"J Immunol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.4049\/jimmunol.1102359","article-title":"Localized production of IL-10 suppresses early inflammatory cell infiltration and subsequent development of IFN-\u03b3-mediated Lyme arthritis","volume":"188","author":"Sonderegger","year":"2012","journal-title":"J Immunol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.molimm.2014.06.010","article-title":"How antibodies use complement to regulate antibody responses","volume":"61","author":"S\u00f6rman","year":"2014","journal-title":"Mol Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e1002066","DOI":"10.1371\/journal.ppat.1002066","article-title":"Lymphoadenopathy during Lyme borreliosis is caused by spirochete migration-induced specific B cell activation","volume":"7","author":"Tunev","year":"2011","journal-title":"PLoS Pathog"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/j.molimm.2009.11.028","article-title":"Binding of the complement inhibitor C4b-binding protein to Lyme disease borreliae","volume":"47","author":"Pietik\u00e4inen","year":"2010","journal-title":"Mol Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2018.00959\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T13:13:23Z","timestamp":1693660403000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2018.00959\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,7]]},"references-count":58,"alternative-id":["10.3389\/fimmu.2018.00959"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2018.00959","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,7]]},"article-number":"959"}}