{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:42:29Z","timestamp":1792197749011,"version":"4.4.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","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","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Lyme disease (LD), the most prevalent tick-borne disease of humans in the Northern Hemisphere, is caused by the spirochetal bacterium of <jats:italic>Borreliella burgdorferi<\/jats:italic> (<jats:italic>Bb<\/jats:italic>) sensu lato complex. In nature, <jats:italic>Bb<\/jats:italic> spirochetes are continuously transmitted between <jats:italic>Ixodes<\/jats:italic> ticks and mammalian or avian reservoir hosts. <jats:italic>Peromyscus leucopus<\/jats:italic> mice are considered the primary mammalian reservoir of <jats:italic>Bb<\/jats:italic> in the United States. Earlier studies demonstrated that experimentally infected <jats:italic>P. leucopus<\/jats:italic> mice do not develop disease. In contrast, C3H mice, a widely used laboratory strain of <jats:italic>Mus musculus<\/jats:italic> in the LD field, develop severe Lyme arthritis. To date, the exact tolerance mechanism of <jats:italic>P. leucopus<\/jats:italic> mice to <jats:italic>Bb<\/jats:italic>-induced infection remains unknown. To address this knowledge gap, the present study has compared spleen transcriptomes of <jats:italic>P. leucopus<\/jats:italic> and C3H\/HeJ mice infected with <jats:italic>Bb<\/jats:italic> strain 297 with those of their respective uninfected controls. Overall, the data showed that the spleen transcriptome of <jats:italic>Bb<\/jats:italic>-infected <jats:italic>P. leucopus<\/jats:italic> mice was much more quiescent compared to that of the infected C3H mice. To date, the current investigation is one of the few that have examined the transcriptome response of natural reservoir hosts to <jats:italic>Borreliella<\/jats:italic> infection. Although the experimental design of this study significantly differed from those of two previous investigations, the collective results of the current and published studies have consistently demonstrated very limited transcriptomic responses of different reservoir hosts to the persistent infection of LD pathogens.<\/jats:p><jats:sec><jats:title>Importance<\/jats:title><jats:p>The bacterium <jats:italic>Borreliella burgdorferi<\/jats:italic> (<jats:italic>Bb<\/jats:italic>) causes Lyme disease, which is one of the emerging and highly debilitating human diseases in countries of the Northern Hemisphere. In nature, <jats:italic>Bb<\/jats:italic> spirochetes are maintained between hard ticks of <jats:italic>Ixodes<\/jats:italic> spp. and mammals or birds. In the United States, the white-footed mouse, <jats:italic>Peromyscus leucopus<\/jats:italic>, is one of the main <jats:italic>Bb<\/jats:italic> reservoirs. In contrast to humans and laboratory mice (e.g., C3H mice), white-footed mice rarely develop clinical signs (disease) despite being (persistently) infected with <jats:italic>Bb<\/jats:italic>. How the white-footed mouse tolerates <jats:italic>Bb<\/jats:italic> infection is the question that the present study has attempted to address. Comparisons of genetic responses between <jats:italic>Bb<\/jats:italic>-infected and uninfected mice demonstrated that, during a long-term <jats:italic>Bb<\/jats:italic> infection, C3H mice reacted much stronger, whereas <jats:italic>P. leucopus<\/jats:italic> mice were relatively unresponsive.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1115350","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T05:50:43Z","timestamp":1681192243000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Comparative transcriptome analysis of Peromyscus leucopus and C3H mice infected with the Lyme disease pathogen"],"prefix":"10.3389","volume":"13","author":[{"given":"Alhussien M.","family":"Gaber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Mandric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Nitirahardjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Piontkivska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E.","family":"Hillhouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Threadgill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Zelikovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem S.","family":"Rogovskyy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/357080a0","article-title":"Molecular and biological characterization of a murine ligand for CD40","volume":"357","author":"Armitage","year":"1992","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"249","DOI":"10.4269\/ajtmh.1992.47.249","article-title":"Carditis in Lyme disease susceptible and resistant strains of laboratory mice infected with Borrelia burgdorferi","volume":"47","author":"Armstrong","year":"1992","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00588-21","article-title":"An infection-tolerant mammalian reservoir for several zoonotic agents broadly counters the inflammatory effects of endotoxin","volume":"12","author":"Balderrama-Gutierrez","year":"2021","journal-title":"mBio"},{"key":"B4","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1099\/00207713-42-3-378","article-title":"Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis","volume":"42","author":"Baranton","year":"1992","journal-title":"Int. J. Syst. Bacteriol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1093\/jme\/tjab055","article-title":"The family Borreliaceae (Spirochaetales), a diverse group in two genera of tick-borne spirochetes of mammals, birds, and reptiles","volume":"58","author":"Barbour","year":"2021","journal-title":"J. Med. Entomol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1093\/infdis\/162.1.133","article-title":"Lyme borreliosis in selected strains and ages of laboratory mice","volume":"162","author":"Barthold","year":"1990","journal-title":"J. Infect. Dis."},{"key":"B7","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","author":"Barthold","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"605","DOI":"10.4269\/ajtmh.1992.47.605","article-title":"Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency","volume":"47","author":"Barthold","year":"1992","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e00434","DOI":"10.1128\/mBio.00434-12","article-title":"Experimental infections of the reservoir species Peromyscus leucopus with diverse strains of Borrelia burgdorferi, a Lyme disease agent","volume":"3","author":"Baum","year":"2012","journal-title":"MBio"},{"key":"B10","doi-asserted-by":"publisher","first-page":"289","DOI":"10.2307\/2346101","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Statist. Soc. Ser. B"},{"key":"B11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.21775\/cimb.042.145","article-title":"Immune response to Borrelia: Lessons from Lyme disease spirochetes","volume":"42","author":"Bockenstedt","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.4049\/jimmunol.173.3.2003","article-title":"MyD88 plays a unique role in host defense but not arthritis development in Lyme disease","volume":"173","author":"Bolz","year":"2004","journal-title":"J. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1084\/jem.183.5.2129","article-title":"CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response","volume":"183","author":"Borrow","year":"1996","journal-title":"J. Exp. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"D1228","DOI":"10.1093\/nar\/gks1147","article-title":"InnateDB: Systems biology of innate immunity and beyond-recent updates and continuing curation","volume":"41","author":"Breuer","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1016\/j.immuni.2013.10.010","article-title":"The spleen in local and systemic regulation of immunity","volume":"39","author":"Bronte","year":"2013","journal-title":"Immunity"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3329","DOI":"10.1128\/iai.67.7.3329-3333.1999","article-title":"Experimental Lyme arthritis in the absence of interleukin-4 or gamma interferon","volume":"67","author":"Brown","year":"1999","journal-title":"Infect. Immun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"5142","DOI":"10.1128\/iai.67.10.5142-5150.1999","article-title":"Dual role of interleukin-10 in murine Lyme disease: Regulation of arthritis severity and host defense","volume":"67","author":"Brown","year":"1999","journal-title":"Infect. Immun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev-immunol-032414-112240","article-title":"Innate immune pattern recognition: A cell biological perspective","volume":"33","author":"Brubaker","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"254","DOI":"10.4269\/ajtmh.1990.42.254","article-title":"Systemic disease in Peromyscus leucopus associated with Borrelia burgdorferi infection","volume":"42","author":"Burgess","year":"1990","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B20","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3109\/00365549309008525","article-title":"Monoclonal antibodies for identification of Borrelia afzelii sp. nov. associated with late cutaneous manifestations of Lyme borreliosis","volume":"25","author":"Canica","year":"1993","journal-title":"Scand. J. Infect. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.ttbdis.2015.04.009","article-title":"Broad diversity of host responses of the white-footed mouse Peromyscus leucopus to Borrelia infection and antigens","volume":"6","author":"Cook","year":"2015","journal-title":"Ticks Tick. Borne Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"7930","DOI":"10.4049\/jimmunol.177.11.7930","article-title":"Gene expression profiling reveals unique pathways associated with differential severity of Lyme arthritis","volume":"177","author":"Crandall","year":"2006","journal-title":"J. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"92","DOI":"10.4269\/ajtmh.1987.36.92","article-title":"Reservoir competence of white-footed mice for Lyme disease spirochetes","volume":"36","author":"Donahue","year":"1987","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B25","doi-asserted-by":"publisher","first-page":"3285","DOI":"10.4049\/jimmunol.158.7.3285","article-title":"Borrelia burgdorferi activates nuclear factor-kappa B and is a potent inducer of chemokine and adhesion molecule gene expression in endothelial cells and fibroblasts","volume":"158","author":"Ebnet","year":"1997","journal-title":"J. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1038\/s41588-019-0470-3","article-title":"CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation","volume":"51","author":"Esteghamat","year":"2019","journal-title":"Nat. Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"D649","DOI":"10.1093\/nar\/gkx1132","article-title":"The reactome pathway knowledgebase","volume":"46","author":"Fabregat","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"40128","DOI":"10.1074\/jbc.M300909200","article-title":"Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter","volume":"278","author":"Friesema","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/s0083-6729(05)70005-4","article-title":"Thyroid hormone transporters","volume":"70","author":"Friesema","year":"2005","journal-title":"Vitam. Horm."},{"key":"B30","doi-asserted-by":"publisher","first-page":"7162","DOI":"10.1128\/iai.68.12.7162-7165.2000","article-title":"Early induction of gamma interferon and interleukin-10 production in draining lymph nodes from mice infected with Borrelia burgdorferi","volume":"68","author":"Ganapamo","year":"2000","journal-title":"Infect. Immun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1128\/aem.01567-07","article-title":"Fitness variation of Borrelia burgdorferi sensu stricto strains in mice","volume":"74","author":"Hanincov\u00e1","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1128\/iai.00969-13","article-title":"MyD88- and TRIF-independent induction of type I interferon drives naive B cell accumulation but not loss of lymph node architecture in Lyme disease","volume":"82","author":"Hastey","year":"2014","journal-title":"Infect. Immun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1111\/j.1749-6632.1988.tb31849.x","article-title":"Immunoglobulin G subclasses specific to Borrelia burgdorferi in patients with Lyme disease","volume":"539","author":"Hechemy","year":"1988","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.4049\/jimmunol.163.5.2382","article-title":"Cutting edge: Inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2","volume":"163","author":"Hirschfeld","year":"1999","journal-title":"J. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"D498","DOI":"10.1093\/nar\/gkz1031","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"616","DOI":"10.3201\/eid2702.202731","article-title":"Estimating the frequency of Lyme disease diagnoses, United States 2010-2018","volume":"27","author":"Kugeler","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/nrmicro1475","article-title":"Fundamental processes in the evolutionary ecology of Lyme borreliosis","volume":"4","author":"Kurtenbach","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00023","article-title":"Immunomodulatory roles of cell cycle regulators","volume":"7","author":"Laphanuwat","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1189\/jlb.0113014","article-title":"Ly6 family proteins in neutrophil biology","volume":"94","author":"Lee","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"355","DOI":"10.4269\/ajtmh.1985.34.355","article-title":"Mice as reservoirs of the Lyme disease spirochete","volume":"34","author":"Levine","year":"1985","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004238","article-title":"Strain-specific variation of the decorin-binding adhesin DbpA influences the tissue tropism of the Lyme disease spirochete","volume":"10","author":"Lin","year":"2014","journal-title":"PloS Pathog."},{"key":"B42","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/s41584-021-00648-5","article-title":"Lyme arthritis: Linking infection, inflammation and autoimmunity","volume":"17","author":"Lochhead","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"eaaw6441","DOI":"10.1126\/sciadv.aaw6441","article-title":"The genome of Peromyscus leucopus, natural host for Lyme disease and other emerging infections","volume":"5","author":"Long","year":"2019","journal-title":"Sci. Adv."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2405","DOI":"10.1128\/iai.01617-14","article-title":"Borrelia burgdorferi RNA induces type I and III interferons via toll-like receptor 7 and contributes to production of NF-\u03baB-dependent cytokines","volume":"82","author":"Love","year":"2014","journal-title":"Infect. Immun."},{"key":"B46","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1128\/iai.66.1.161-168.1998","article-title":"Distinct characteristics of resistance to Borrelia burgdorferi-induced arthritis in C57BL\/6N mice","volume":"66","author":"Ma","year":"1998","journal-title":"Infect. Immun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/ni.1733","article-title":"Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells","volume":"10","author":"Mancuso","year":"2009","journal-title":"Nat. Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"5190","DOI":"10.1128\/iai.68.9.5190-5197.2000","article-title":"T-cell-independent responses to Borrelia burgdorferi are critical for protective immunity and resolution of Lyme disease","volume":"68","author":"McKisic","year":"2000","journal-title":"Infect. Immun."},{"key":"B49","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.idc.2015.02.010","article-title":"Epidemiology of Lyme disease","volume":"29","author":"Mead","year":"2015","journal-title":"Infect. Dis. Clin. North Am."},{"key":"B50","doi-asserted-by":"publisher","first-page":"8492","DOI":"10.4049\/jimmunol.181.12.8492","article-title":"A critical role for type I IFN in arthritis development following Borrelia burgdorferi infection of mice","volume":"181","author":"Miller","year":"2008","journal-title":"J. Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"155","DOI":"10.7589\/0090-3558-30.2.155","article-title":"Experimental Borrelia burgdorferi infection in Peromyscus leucopus","volume":"30","author":"Moody","year":"1994","journal-title":"J. Wildl. Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"3240","DOI":"10.4049\/jimmunol.137.10.3240","article-title":"Role of Ly-6 in lymphocyte activation. I. Characterization of a monoclonal of a monoclonal antibody to a nonpolymorphic Ly-6 specificity","volume":"137","author":"Ortega","year":"1986","journal-title":"J. Immunol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.neulet.2018.01.058","article-title":"Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure","volume":"671","author":"Parthasarathy","year":"2018","journal-title":"Neurosci. Lett."},{"key":"B54","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":"B55","doi-asserted-by":"publisher","first-page":"5279","DOI":"10.4049\/jimmunol.0901390","article-title":"Recognition of Borrelia burgdorferi, the Lyme disease spirochete, by TLR7 and TLR9 induces a type I IFN response by human immune cells","volume":"183","author":"Petzke","year":"2009","journal-title":"J. Immunol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12866-016-0644-4","article-title":"Borrelia burgdorferi induces a type I interferon response during early stages of disseminated infection in mice","volume":"16","author":"Petzke","year":"2016","journal-title":"BMC Microbio.l"},{"key":"B57","doi-asserted-by":"publisher","first-page":"S191","DOI":"10.1017\/s0031182003004694","article-title":"Lyme borreliosis in Europe and north America","author":"Piesman","year":"2004","journal-title":"Parasitology"},{"key":"B58","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","article-title":"Defective LPS signaling in C3H\/HeJ and C57BL\/10ScCr mice: Mutations in Tlr4 gene","volume":"282","author":"Poltorak","year":"1998","journal-title":"Science"},{"key":"B59","doi-asserted-by":"publisher","first-page":"2943","DOI":"10.1093\/bioinformatics\/btac166","article-title":"Analysing high-throughput sequencing data in Python with HTSeq 2.0","volume":"38","author":"Putri","year":"2022","journal-title":"Bioinformatics"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1111\/j.1420-9101.2012.02515.x","article-title":"Infection intensity and infectivity of the tick-borne pathogen Borrelia afzelii","volume":"25","author":"Raberg","year":"2012","journal-title":"J. Evol. Biol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"333","DOI":"10.21775\/cimb.042.333","article-title":"Lyme disease in humans","volume":"42","author":"Radolf","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124268","article-title":"Evaluation of the importance of VlsE antigenic variation for the enzootic cycle of Borrelia burgdorferi","volume":"10","author":"Rogovskyy","year":"2015","journal-title":"PloS One"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e00890","DOI":"10.1128\/IAI.00890-16","article-title":"Antibody response to Lyme disease spirochetes in the context of VlsE-mediated immune evasion","volume":"85","author":"Rogovskyy","year":"2016","journal-title":"Infect. Immun."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1002\/cphy.c200003","article-title":"The role of thyroid hormone in the innate and adaptive immune response during infection","volume":"10","author":"Rubingh","year":"2020","journal-title":"Compr. Physiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3445","DOI":"10.1128\/iai.57.11.3445-3451.1989","article-title":"Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi)","volume":"57","author":"Schwan","year":"1989","journal-title":"Infect. Immun."},{"key":"B66","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1089\/vbz.2009.0215","article-title":"Borrelia burgdorferi has minimal impact on the Lyme disease reservoir host Peromyscus leucopus","volume":"11","author":"Schwanz","year":"2011","journal-title":"Vector Borne Zoonotic Dis."},{"key":"B67","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1128\/iai.01600-07","article-title":"Distinct roles for MyD88 and toll-like receptors 2, 5, and 9 in phagocytosis of Borrelia burgdorferi and cytokine induction","volume":"76","author":"Shin","year":"2008","journal-title":"Infect. Immun."},{"key":"B68","doi-asserted-by":"publisher","first-page":"3461","DOI":"10.1093\/bioinformatics\/btx441","article-title":"Reactome enhanced pathway visualization","volume":"33","author":"Sidiropoulos","year":"2017","journal-title":"Bioinformatics"},{"key":"B69","doi-asserted-by":"publisher","first-page":"91","DOI":"10.5435\/00124635-201102000-00004","article-title":"Lyme disease and the orthopaedic implications of Lyme arthritis","volume":"19","author":"Smith","year":"2011","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"B70","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":"B71","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"10800","DOI":"10.1093\/nar\/gkab835","article-title":"Correction to \u2018The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets\u2019","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1128\/iai.55.9.2311-2313.1987","article-title":"Absence of lipopolysaccharide in the Lyme disease spirochete, Borrelia burgdorferi","volume":"55","author":"Takayama","year":"1987","journal-title":"Infect. Immun."},{"key":"B75","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1002\/eji.1830180616","article-title":"Ly-6 A\/E antigen of murine T cells is associated with a distinct pathway of activation. requirements for interferon and exogenous interleukin 2","volume":"18","author":"Toulon","year":"1988","journal-title":"Eur. J. Immunol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0065-2776(08)60865-2","article-title":"CD40-CD40 ligand: A multifunctional receptor-ligand pair","volume":"61","author":"Van Kooten","year":"1996","journal-title":"Adv. Immunol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1684\/ecn.2017.0396","article-title":"The role of host immune cells and Borrelia burgdorferi antigens in the etiology of Lyme disease","volume":"28","author":"Verhaegh","year":"2017","journal-title":"Eur. Cytokine Netw."},{"key":"B78","doi-asserted-by":"publisher","first-page":"D433","DOI":"10.1093\/nar\/gki005","article-title":"STRING: Known and predicted protein-protein associations, integrated and transferred across organisms","volume":"33","author":"von Mering","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"B79","doi-asserted-by":"publisher","first-page":"348","DOI":"10.4049\/jimmunol.168.1.348","article-title":"Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi","volume":"168","author":"Wooten","year":"2002","journal-title":"J. Immunol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1089\/153036602321653860","article-title":"Toll-like receptor 2 plays a pivotal role in host defense and inflammatory response to Borrelia burgdorferi","volume":"2","author":"Wooten","year":"2002","journal-title":"Vector Borne Zoonotic Dis."},{"key":"B81","doi-asserted-by":"publisher","first-page":"4584","DOI":"10.4049\/jimmunol.157.10.4584","article-title":"Borrelia burgdorferi outer membrane protein a induces nuclear translocation of nuclear factor-kappa b and inflammatory activation in human endothelial cells","volume":"157","author":"Wooten","year":"1996","journal-title":"J. Immunol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/s1369-5274(00)00202-2","article-title":"Host-pathogen interactions promoting inflammatory Lyme arthritis: Use of mouse models for dissection of disease processes","volume":"4","author":"Wooten","year":"2001","journal-title":"Curr. Opin. Microbiol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nature08512","article-title":"HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses","volume":"462","author":"Yanai","year":"2009","journal-title":"Nature"},{"key":"B84","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/cmi.2011.47","article-title":"Bone marrow and the control of immunity","volume":"9","author":"Zhao","year":"2012","journal-title":"Cell Mol. Immunol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"6421","DOI":"10.1002\/ece3.6377","article-title":"Comparison of spleen transcriptomes of two wild rodent species reveals differences in the immune response against Borrelia afzelii","volume":"10","author":"Zhong","year":"2020","journal-title":"Eco.l Evol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.ttbdis.2019.03.017","article-title":"Colonization and pathology of Borrelia afzelii in its natural hosts","volume":"10","author":"Zhong","year":"2019","journal-title":"Ticks Tick Borne Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1115350\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T05:50:49Z","timestamp":1681192249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2023.1115350\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,11]]},"references-count":86,"alternative-id":["10.3389\/fcimb.2023.1115350"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2023.1115350","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,11]]},"article-number":"1115350"}}