2025
Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice
Yu Q, Tang X, Hart T, Homer R, Belperron A, Bockenstedt L, Ring A, Nakamura A, Fikrig E. Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice. ELife 2025, 14: rp104913. PMID: 40392222, PMCID: PMC12092001, DOI: 10.7554/elife.104913.Peer-Reviewed Original ResearchConceptsSecretory leukocyte protease inhibitorJoint inflammationC57BL/6 miceHigher infection loadTick-borne infectionsWild-type control miceClinical manifestations of infectionDevelopment of Lyme arthritisElevated serum levelsExcessive pro-inflammatory responsesManifestations of infectionProtease inhibitorsPro-inflammatory responseAnkle joint tissueInfection loadPromote tissue repairAnti-inflammatory effectsSerum levelsPeriarticular swellingClinical manifestationsControl miceTibiotarsal jointMMP-8Lyme diseaseIL-6Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice
Yu Q, Tang X, Hart T, Homer R, Belperron A, Bockenstedt L, Ring A, Nakamura A, Fikrig E. Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice. ELife 2025, 14 DOI: 10.7554/elife.104913.4.Peer-Reviewed Original ResearchSecretory leukocyte protease inhibitorSLPI-deficient miceJoint inflammationC57BL/6 miceDeficient miceB. burgdorferiHigher infection loadTick-borne infectionsWild-type control miceDeficient C57BL/6 miceClinical manifestations of infectionDevelopment of Lyme arthritisElevated serum levelsExcessive pro-inflammatory responsesManifestations of infectionProtease inhibitorsPro-inflammatory responseAnkle joint tissueInfection loadPromote tissue repairAnti-inflammatory effectsSerum levelsPeriarticular swellingClinical manifestationsControl miceTick feeding or vaccination with tick antigens elicits immunity to the Ixodes scapularis exoproteome in guinea pigs and humans
Hart T, Cui Y, Telford S, Marín-López A, Calloway K, Dai Y, Matias J, DePonte K, Jaycox J, DeBlasio M, Hoornstra D, Belperron A, Cibichakravarthy B, Johnson E, Alameh M, Dwivedi G, Hovius J, Bockenstedt L, Weissman D, Ring A, Fikrig E. Tick feeding or vaccination with tick antigens elicits immunity to the Ixodes scapularis exoproteome in guinea pigs and humans. Science Translational Medicine 2025, 17: eads9207. PMID: 40138454, PMCID: PMC12067475, DOI: 10.1126/scitranslmed.ads9207.Peer-Reviewed Original ResearchConceptsTick antigensTick resistanceVector of tick-borne pathogensAcquired tick resistanceTick-borne pathogensIxodes scapularis</i>Tick feedingAntitick vaccinesDetectable antibody responseGuinea pigsTicksTick bitesAntigen cocktailPigsPrimary vectorFeedingAntibody responseHumoral responseImmunogen candidateAntigenLyme diseaseImmunoglobulin GRepeated exposureIxodesNorth America
2024
Insights From Omics in Lyme Disease
Bockenstedt L, Belperron A. Insights From Omics in Lyme Disease. The Journal Of Infectious Diseases 2024, 230: s18-s26. PMID: 39140719, PMCID: PMC12102470, DOI: 10.1093/infdis/jiae250.Peer-Reviewed Original Research491 Novel characteristics of memory B cells identified by single-cell immunophenotyping of erythema migrans skin lesions
Jiang R, Kleinstein S, Bockenstedt L. 491 Novel characteristics of memory B cells identified by single-cell immunophenotyping of erythema migrans skin lesions. Journal Of Investigative Dermatology 2024, 144: s85. DOI: 10.1016/j.jid.2024.06.507.Peer-Reviewed Original ResearchCombining short- and long-read sequencing unveils geographically structured diversity in Borrelia miyamotoi
Hoornstra D, Kuleshov K, Fingerle V, Hepner S, Wagemakers A, Strube C, Castillo-Ramírez S, Bockenstedt L, Telford S, Sprong H, Platonov A, Margos G, Hovius J. Combining short- and long-read sequencing unveils geographically structured diversity in Borrelia miyamotoi. IScience 2024, 27: 110616. PMID: 39262806, PMCID: PMC11388275, DOI: 10.1016/j.isci.2024.110616.Peer-Reviewed Original ResearchComparative whole-genome sequencingCombination of IlluminaLong-read sequencingGenetically distinct populationsGenome assemblyPacBio platformPlasmid typesCore plasmidHuman pathogensGenetic basisDistinct populationsExpression sitesPlasmidGeographical originIxodes speciesGenomeIsolatesTick-borne human pathogenVector competenceStructural diversityNorth AmericaBorrelia miyamotoiPacBioIlluminaVirulence
2023
Proteome Analysis for Inflammation Related to Acute and Convalescent Infection
Sigdel T, Sur S, Boada P, McDermott S, Arlehamn C, Murray K, Bockenstedt L, Kerwin M, Reed E, Harris E, Stuart K, Peters B, Sesma A, Montgomery R, Sarwal M. Proteome Analysis for Inflammation Related to Acute and Convalescent Infection. Inflammation 2023, 47: 346-362. PMID: 37831367, PMCID: PMC10799112, DOI: 10.1007/s10753-023-01913-3.Peer-Reviewed Original ResearchC motif chemokine ligand 1C motif chemokine receptor 7Human Immunology Project ConsortiumWest Nile virusDengue virusLyme diseaseKidney transplant patientsChemokine ligand 1Chemokine receptor 7Common therapeutic interventionTumor necrosis factor receptorHost defense mechanismsNecrosis factor receptorCell surface markersConvalescent infectionTransplant patientsConvalescent phaseImmune signaturesAcute phaseConvalescent stageReceptor 7Common biological pathwaysHealthy donorsPolyomavirus infectionImmune response
2022
Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection
Boada P, Fatou B, Belperron A, Sigdel T, Smolen K, Wurie Z, Levy O, Ronca S, Murray K, Liberto J, Rashmi P, Kerwin M, Montgomery R, Bockenstedt L, Steen H, Sarwal M. Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection. Frontiers In Immunology 2022, 13: 1012824. PMID: 36569838, PMCID: PMC9784464, DOI: 10.3389/fimmu.2022.1012824.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionLyme diseaseVirus infectionWNV infectionSerum proteomeSymptomatic WNV infectionTime of diagnosisHealthy control seraDisseminated Lyme diseaseHost response pathwaysExtracellular bacterial infectionsSerum proteomic analysisIntracellular viral infectionsViral infectionHost responseBacterial infectionsControl seraStudy participantsInfectionDiseaseDisease biomarkersEarly diagnosticsLC/MSMolecular mechanismsRecovery phase
2021
Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes
Bockenstedt L, Wooten R, Baumgarth N. Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes. 2021 DOI: 10.21775/9781913652616.18.Chapters
2017
Chapter 110 Lyme Disease
Bockenstedt L. Chapter 110 Lyme Disease. 2017, 1891-1904.e4. DOI: 10.1016/b978-0-323-31696-5.00110-8.Chapters
2016
A Tribute to James N. Miller
Bockenstedt L. A Tribute to James N. Miller. Onco Therapeutics 2016, 7: 163-164. DOI: 10.1615/forumimmundisther.2017020474.Peer-Reviewed Original Research
2013
In Memoriam: Stephen E. Malawista, MD, 1934–2013
Montgomery R, Bucala R, Bockenstedt L. In Memoriam: Stephen E. Malawista, MD, 1934–2013. Arthritis & Rheumatology 2013, 66: 1-1. DOI: 10.1002/art.38233.Commentaries, Editorials and Letters110 Lyme Disease
Bockenstedt L. 110 Lyme Disease. 2013, 1815-1828.e3. DOI: 10.1016/b978-1-4377-1738-9.00110-9.Chapters
2012
Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy
Bockenstedt LK, Gonzalez DG, Haberman AM, Belperron AA. Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. Journal Of Clinical Investigation 2012, 122: 2652-2660. PMID: 22728937, PMCID: PMC3386809, DOI: 10.1172/jci58813.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsAntigens, BacterialArthritis, InfectiousBacterial LoadBorrelia burgdorferiCartilageCeftriaxoneDoxycyclineEar, ExternalFemaleFluorescence Recovery After PhotobleachingGreen Fluorescent ProteinsJoint CapsuleLyme DiseaseMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutMicroscopy, Fluorescence, MultiphotonMyeloid Differentiation Factor 88PatellaRecombinant ProteinsConceptsNaive miceAntibiotic treatmentIntravital microscopyAntibiotic-refractory Lyme arthritisLyme diseaseTNF-α productionBorrelia burgdorferi antigensB. burgdorferi antigensSpirochete antigenTLR responsivenessInflammatory arthritisAntibiotic therapyLyme arthritisWT miceMusculoskeletal symptomsAntigens persistSlow resolutionImmunodeficient miceMouse modelTissue transplantsPathogen burdenSpirochete DNAInfectious spirochetesLyme borreliosisMiceThe heterogeneous motility of the Lyme disease spirochete in gelatin mimics dissemination through tissue
Harman MW, Dunham-Ems SM, Caimano MJ, Belperron AA, Bockenstedt LK, Fu HC, Radolf JD, Wolgemuth CW. The heterogeneous motility of the Lyme disease spirochete in gelatin mimics dissemination through tissue. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 3059-3064. PMID: 22315410, PMCID: PMC3286914, DOI: 10.1073/pnas.1114362109.Peer-Reviewed Original Research
2011
Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly
Qian F, Wang X, Zhang L, Chen S, Piecychna M, Allore H, Bockenstedt L, Malawista S, Bucala R, Shaw AC, Fikrig E, Montgomery RR. Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell 2011, 11: 104-110. PMID: 22023165, PMCID: PMC3257374, DOI: 10.1111/j.1474-9726.2011.00759.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingExtracellular Signal-Regulated MAP KinasesFemaleHumansInflammationInterleukin-8MaleMiddle AgedMonocytesMultivariate AnalysisNF-kappa Bp38 Mitogen-Activated Protein KinasesPhosphorylationProtein TransportRNA, MessengerSignal TransductionToll-Like Receptor 5Tumor Necrosis Factor-alphaConceptsToll-like receptorsIL-8Multivariable mixed-effects modelsOlder individualsElevated IL-8Levels of TLR5Expression of TLR5Production of TNFAge-associated elevationAge-related decreaseDendritic cellsImmune responsivenessElderly donorsInflammatory responseImmune functionNF-κBTLR5Progressive declineMonocytesMixed effects modelsMAPK p38Significant increaseEffects modelAssociated increaseCritical mechanismBallistic Motion of Spirochete Membrane Proteins
Kress H, Boltyanskiy R, Belperron A, Mejean C, Wolgemuth C, Bockenstedt L, Dufresne E. Ballistic Motion of Spirochete Membrane Proteins. Biophysical Journal 2011, 100: 515a. DOI: 10.1016/j.bpj.2010.12.3013.Peer-Reviewed Original ResearchThe impact of nanoparticle ligand density on dendritic-cell targeted vaccines
Bandyopadhyay A, Fine RL, Demento S, Bockenstedt LK, Fahmy TM. The impact of nanoparticle ligand density on dendritic-cell targeted vaccines. Biomaterials 2011, 32: 3094-3105. PMID: 21262534, PMCID: PMC4570971, DOI: 10.1016/j.biomaterials.2010.12.054.Peer-Reviewed Original ResearchConceptsIL-10 responsesDEC-205 receptorIL-10Cytokine responsesT cellsSubsequent T cell responsesBlockade of CD36T cell responsesAntigen delivery systemDifferential cytokine responsesScavenger receptor CD36Vaccine delivery systemDC expressionVaccine efficacyDC functionDC productionReceptor CD36Cell responsesDelivery systemOVA nanoparticlesDelivery of therapeuticsCD36AntigenReceptorsSimilar pattern
2009
The Caspase 1 Inflammasome Is Not Required for Control of Murine Lyme Borreliosis
Liu N, Belperron AA, Booth CJ, Bockenstedt LK. The Caspase 1 Inflammasome Is Not Required for Control of Murine Lyme Borreliosis. Infection And Immunity 2009, 77: 3320-3327. PMID: 19487481, PMCID: PMC2715671, DOI: 10.1128/iai.00100-09.Peer-Reviewed Original ResearchConceptsCaspase-1 inflammasomeCaspase-1Immune responseHost defenseLyme borreliosisToll-like receptor-mediated responsesDay 14 postinfectionPrevalence of arthritisT cell responsesApoptosis-associated speck-like proteinMild transient elevationBorrelia burgdorferiMurine Lyme borreliosisReceptor-mediated responsesCaspase-1 deficiencyC-terminal caspase recruitment domainSpeck-like proteinAbility of macrophagesEnzyme caspase-1IL-18Humoral immunityInterleukin-1betaTransient elevationPathogen burdenInflammasomeLangerhans Cell Deficiency Impairs Ixodes scapularis Suppression of Th1 Responses in Mice
Vesely DL, Fish D, Shlomchik MJ, Kaplan DH, Bockenstedt LK. Langerhans Cell Deficiency Impairs Ixodes scapularis Suppression of Th1 Responses in Mice. Infection And Immunity 2009, 77: 1881-1887. PMID: 19273564, PMCID: PMC2681756, DOI: 10.1128/iai.00030-09.Peer-Reviewed Original ResearchConceptsTh1 responseTick salivaLangerhans cell subsetsLC-deficient miceSkin dendritic cellsTh1 immune responseTh cell polarizationTh cell responsesRegional lymph nodesT cell responsesTick feedingSecondary lymphoid organsGamma interferon productionSpleens of miceWild-type miceIxodes scapularis ticksT helperDendritic cellsLymph nodesLN cellsCell subsetsImmunomodulatory effectsLymphoid organsTh2 cellsImmune response
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