{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:28:34Z","timestamp":1790166514270,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UWM College of Health Sciences SPARC Award","award":["AAB1553"],"award-info":[{"award-number":["AAB1553"]}]},{"name":"UWM College of Health Sciences SPARC Award","award":["101X353"],"award-info":[{"award-number":["101X353"]}]},{"name":"UWM Research Growth Initiative Award","award":["AAB1553"],"award-info":[{"award-number":["AAB1553"]}]},{"name":"UWM Research Growth Initiative Award","award":["101X353"],"award-info":[{"award-number":["101X353"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>We previously demonstrated that a depletion of regulatory T (Treg) cells in Lyme arthritis-resistant C57BL\/6 mice leads to pathological changes in the tibiotarsal joints following infection with Borrelia burgdorferi. Here, we assessed the effects of Treg cells on the response to B. burgdorferi infection in BALB\/c mice, which exhibit infection-dose-dependent disease and a different sequence of immune events than C57BL\/6 mice. The depletion of Treg cells prior to infection with 1 \u00d7 102, but not 5 \u00d7 103, organisms led to increased swelling of the tibiotarsal joints. However, Treg cell depletion did not significantly affect the development of histopathology at these low doses of infection. BALB\/c mice depleted of Treg cells before infection with 1 \u00d7 103 spirochetes harbored a higher borrelial load in the hearts and exhibited higher levels of serum interleukin-10 five weeks later. These results indicate that Treg cells regulate certain aspects of the response to B. burgdorferi in a mouse strain that may display a range of disease severities. As the presentation of Lyme disease may vary among humans, it is necessary to consider multiple animal models to obtain a complete picture of the various means by which Treg cells affect the host response to B. burgdorferi.<\/jats:p>","DOI":"10.3390\/pathogens12020189","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T01:30:30Z","timestamp":1674696630000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Regulatory T Cell Depletion in BALB\/c Mice Infected with Low Doses of Borrelia burgdorferi"],"prefix":"10.3390","volume":"12","author":[{"given":"Kaitlyn N.","family":"Santiago","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Wisconsin\u2013Milwaukee, Milwaukee, WI 53211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Kozlik","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Wisconsin\u2013Milwaukee, Milwaukee, WI 53211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S.","family":"Liedhegner","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Wisconsin\u2013Milwaukee, Milwaukee, WI 53211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0276-2522","authenticated-orcid":false,"given":"Rebecca A.","family":"Slick","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Clinical and Translational Science Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean T.","family":"Nardelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Wisconsin\u2013Milwaukee, Milwaukee, WI 53211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","unstructured":"Lochhead, R.B., Ma, Y., Zachary, J.F., Baltimore, D., Zhao, J.L., Weis, J.H., O\u2019Connell, R.M., and Weis, J.J. (2014). MicroRNA-146a provides feedback regulation of Lyme arthritis but not carditis during infection with Borrelia burgdorferi. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004212"},{"key":"ref_3","first-page":"1075","article-title":"Association of CD4+ CD25+ T cells with prevention of severe destructive arthritis in Borrelia. burgdorferi-vaccinated and challenged gamma interferon-deficient mice treated with anti-interleukin-17 antibody","volume":"11","author":"Nardelli","year":"2004","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_4","first-page":"786","article-title":"CD4+ CD25+ T cells prevent arthritis associated with Borrelia vaccination and infection","volume":"12","author":"Nardelli","year":"2005","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1128\/CVI.00137-06","article-title":"Anti-CD25 antibody treatment of mice vaccinated and challenged with Borrelia spp. does not exacerbate arthritis but inhibits borreliacidal antibody production","volume":"13","author":"Nardelli","year":"2006","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1002\/art.27468","article-title":"Treg cell numbers and function in patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis","volume":"62","author":"Shen","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00160-20","DOI":"10.1128\/IAI.00160-20","article-title":"Regulatory T cells contribute to resistance against Lyme arthritis","volume":"88","author":"Siebers","year":"2020","journal-title":"Infect. Immun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1084\/jem.20061852","article-title":"Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease","volume":"204","author":"Lahl","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","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":"ref_10","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S1074-7613(02)00365-5","article-title":"In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens","volume":"17","author":"Jung","year":"2002","journal-title":"Immunity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1111\/j.1365-2958.2012.08160.x","article-title":"The \u03b23-integrin ligand of Borrelia. burgdorferi is critical for infection of mice but not ticks","volume":"85","author":"Ristow","year":"2012","journal-title":"Mol. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1128\/IAI.71.6.3437-3442.2003","article-title":"Inhibition of interleukin-17 prevents the development of arthritis in vaccinated mice challenged with Borrelia burgdorferi","volume":"71","author":"Burchill","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1128\/JCM.37.4.987-992.1999","article-title":"Rapid and sensitive quantification of Borrelia. burgdorferi-infected mouse tissues by continuous fluorescent monitoring of PCR","volume":"37","author":"Morrison","year":"1999","journal-title":"J. Clin. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1128\/jcm.25.4.600-604.1987","article-title":"Detection of antibody to murine cytomegalovirus by enzyme-linked immunosorbent and indirect immunofluorescence assays","volume":"25","author":"Classen","year":"1987","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","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":"ref_16","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1126\/science.1079490","article-title":"Control of regulatory T cell development by the transcription factor Foxp3","volume":"299","author":"Hori","year":"2003","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-1-61737-979-6_10","article-title":"In vivo depletion of FoxP3+ Tregs using the DEREG mouse model","volume":"707","author":"Lahl","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jim.2014.03.005","article-title":"Limitations of Foxp3+ Treg depletion following viral infection in DEREG mice","volume":"406","author":"Christiaansen","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1002\/art.37910","article-title":"Dysregulation of CD4+CD25high T cells in the synovial fluid of patients with antibiotic-refractory Lyme arthritis","volume":"65","author":"Vudattu","year":"2013","journal-title":"Arthritis Rheum"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5603","DOI":"10.1128\/IAI.68.10.5603-5609.2000","article-title":"Interleukin-4 (IL-4) and IL-13 signaling pathways do not regulate Borrelia. burgdorferi-induced arthritis in mice: IgG1 is not required for host control of tissue spirochetes","volume":"68","author":"Potter","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1189\/jlb.0604341","article-title":"BALB\/c mice have more CD4+CD25 regulatory T cells and show greater susceptibility to suppression of their CD4+CD25- responder T cells than C57BL\/6 mice","volume":"78","author":"Chen","year":"2005","journal-title":"J. Leuk. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1084\/jem.181.2.713","article-title":"T cell genetic background determines default T helper phenotype development in vitro","volume":"181","author":"Hsieh","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1084\/jem.174.3.593","article-title":"Borrelia. burgdorferi activates a T helper type 1-like T cell subset in Lyme arthritis","volume":"174","author":"Yssel","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.4049\/jimmunol.160.2.1022","article-title":"T helper 1 response is dominant and localized to the synovial fluid in patients with Lyme arthritis","volume":"160","author":"Gross","year":"1998","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1002\/art.34383","article-title":"Association of a Toll-like receptor 1 polymorphism with heightened Th1 inflammatory responses and antibiotic-refractory Lyme arthritis","volume":"64","author":"Strle","year":"2012","journal-title":"Arthritis Rheum"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.4049\/jimmunol.155.4.2020","article-title":"Role of IL-4 and IFN-\u03b3 in modulation of immunity to Borrelia. burgdorferi in mice","volume":"155","author":"Nickell","year":"1995","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/art.1780400111","article-title":"T cell cytokine pattern in the joints of patients with Lyme arthritis and its regulation by cytokines and anticytokines","volume":"40","author":"Yin","year":"1997","journal-title":"Arthritis Rheum"},{"key":"ref_28","doi-asserted-by":"crossref","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":"ref_29","doi-asserted-by":"crossref","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":"ref_30","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1182\/blood-2003-09-3302","article-title":"Th2 cells are less susceptible than Th1 cells to the suppressive activity of CD25+ regulatory thymocytes because of their responsiveness to different cytokines","volume":"103","author":"Cosmi","year":"2004","journal-title":"Blood"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/2\/189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:15:43Z","timestamp":1760120143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/2\/189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["pathogens12020189"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12020189","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,25]]}}}