2025
Bacterial and host enzymes modulate the pro-inflammatory response elicited by the peptidoglycan of Lyme disease agent Borrelia burgdorferi
McCausland J, Kloos Z, Irnov I, Sonnert N, Zhou J, Putnik R, Mueller E, Steere A, Palm N, Grimes C, Jacobs-Wagner C. Bacterial and host enzymes modulate the pro-inflammatory response elicited by the peptidoglycan of Lyme disease agent Borrelia burgdorferi. PLOS Pathogens 2025, 21: e1013324. PMID: 40623106, PMCID: PMC12279116, DOI: 10.1371/journal.ppat.1013324.Peer-Reviewed Original ResearchConceptsImmune responsePost-antibiotic treatmentProinflammatory immune responseNOD2-dependent immune responsesPro-inflammatory responseHost sensingAntibiotic therapyPersistent arthritisImmune detectionImmune systemHuman cell linesCell linesSpirochete Borrelia burgdorferiB. burgdorferiLyme disease agent Borrelia burgdorferiPatientsDown Syndrome Alters Type-III IFN and Pro-Inflammatory Airway Epithelial Responses to RSV Infection.
Chorvinsky E, Bhattacharya S, Bera B, Welham A, Ismat K, Lawlor C, Preciado D, Gomez J, Morizono H, Pillai D, Gutierrez M, Jaiswal J, Nino G. Down Syndrome Alters Type-III IFN and Pro-Inflammatory Airway Epithelial Responses to RSV Infection. American Journal Of Respiratory Cell And Molecular Biology 2025 PMID: 40587878, DOI: 10.1165/rcmb.2025-0068oc.Peer-Reviewed Original ResearchAirway epithelial cellsRSV infectionType III IFNsViral infectionDown syndromeNasal airway epithelial cellsResponse to RSV infectionSeverity of RSV infectionRSV-induced responsesSevere viral bronchiolitisAirway immune responsesRespiratory syncytial virusPro-inflammatory statePro-inflammatory cytokinesPro-inflammatory responseEnhanced viral infectionType III IFN responseViral bronchiolitisSyncytial virusImmunological basisPediatric donorsPrimary sitePro-inflammatoryImmune responseEpithelial cellsSecretory 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 miceTNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair potential in degenerative conditions
Gansau J, Grossi E, Rodriguez L, Wang M, Laudier D, Chaudhary S, Hecht A, Fu W, Sebra R, Liu C, Iatridis J. TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair potential in degenerative conditions. Osteoarthritis And Cartilage 2025, 33: 874-887. PMID: 40139648, PMCID: PMC12146073, DOI: 10.1016/j.joca.2025.02.791.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnnulus FibrosusCells, CulturedCellular SenescenceCulture Media, ConditionedFemaleHumansIntervertebral DiscIntervertebral Disc DegenerationMaleMiddle AgedReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IISignal TransductionTumor Necrosis Factor-alphaConceptsTNFR2 signalingConditioned mediumInflammatory responseIVD cellsHuman annulus fibrosusDelivery of macrophagesPainful intervertebral discIntervertebral discAttenuated inflammatory responsePro-inflammatory responseNO effectHuman IVD cellsHuman annulus fibrosus cellsReduced metabolic rateReceptor 2Cytokine mixtureMacrophage populationsHAFS cellsInflammatory proteinsMetabolic impairmentBulk RNA-seqIntervertebral disc repairMetabolic rateCell cycle stateAutopsy subjects
2023
Adiponectin in the mammalian host influences ticks’ acquisition of the Lyme disease pathogen Borrelia
Tang X, Cao Y, Booth C, Arora G, Cui Y, Matias J, Fikrig E. Adiponectin in the mammalian host influences ticks’ acquisition of the Lyme disease pathogen Borrelia. PLOS Biology 2023, 21: e3002331. PMID: 37862360, PMCID: PMC10619873, DOI: 10.1371/journal.pbio.3002331.Peer-Reviewed Original ResearchConceptsAdipocyte-derived hormoneBite siteAdiponectin-deficient miceInfiltration of neutrophilsTick bite sitePro-inflammatory responseWild-type animalsIxodes scapularis ticksIL-1βVascular leakageHistamine releaseTick biteAdiponectinInfectious diseasesLyme disease agentBlood feeding arthropodsBorrelia burgdorferiScapularis ticksAnimal infectious diseasesBlood feedingB. burgdorferi survivalHuman bloodHormonePathogen acquisitionMammalian hostsLeishmania major-derived lipophosphoglycan influences the host’s early immune response by inducing platelet activation and DKK1 production via TLR1/2
Ihedioha O, Sivakoses A, Beverley S, McMahon-Pratt D, Bothwell A. Leishmania major-derived lipophosphoglycan influences the host’s early immune response by inducing platelet activation and DKK1 production via TLR1/2. Frontiers In Immunology 2023, 14: 1257046. PMID: 37885890, PMCID: PMC10598878, DOI: 10.3389/fimmu.2023.1257046.Peer-Reviewed Original ResearchConceptsLeukocyte-platelet aggregatesEarly immune responseImmune responsePlatelet activationHost's early immune responseCell-mediated immune responsesTh2 cell polarizationAdaptive immune responsesPro-inflammatory responsePattern recognition receptorsKey virulence factorsRecognition receptorsInfectious diseasesPathogenic moleculesEndothelial cellsWnt antagonistsInfection siteVirulence factorsTLR1/2PlateletsDickkopf1Cell typesLipophosphoglycanActivationResponseElevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes
Li Z, Zhao M, Li J, Luo W, Huang J, Huang G, Xie Z, Xiao Y, Huang J, Li X, Zhao B, Zhou Z. Elevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes. Clinical Immunology 2023, 255: 109729. PMID: 37562723, DOI: 10.1016/j.clim.2023.109729.Peer-Reviewed Original ResearchConceptsType 1 diabetesPro-inflammatory responseB cellsGlucose metabolismCytokine productionAberrant B cell responsesNon-obese diabetic (NOD) micePro-inflammatory cytokine productionHigh blood glucose levelsOnset of diabetesInflammatory cytokine productionAdaptive immune responsesB cell responsesCross-sectional cohortImmune system failureDiabetic mouse modelB cell functionBlood glucose levelsB cell populationsB cell metabolismPancreatic beta cellsB cell proliferationElevated glucose metabolismInsulitis developmentNOD mice
2022
Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
Fourati S, Tomalin LE, Mulè MP, Chawla DG, Gerritsen B, Rychkov D, Henrich E, Miller HER, Hagan T, Diray-Arce J, Dunn P, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Pulendran B, Kleinstein S, Sékaly R. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination. Nature Immunology 2022, 23: 1777-1787. PMID: 36316476, PMCID: PMC9747610, DOI: 10.1038/s41590-022-01329-5.Peer-Reviewed Original ResearchConceptsAntibody responsePro-inflammatory response genesToll-like receptor ligandsBlood transcriptional profilesHigher serum antibodyPro-inflammatory responseSerum antibodiesDifferent vaccinesImmune responseImmune stateMetabolism alterationsEndotypesImmune systemVaccinationReceptor ligandsCell proliferationGene expression characteristicsActivation stateDifferential expressionTranscriptional profilesResponse genesExpression characteristicsResponseWide variationAdjuvant
2020
CTIM-18. DENDRITIC CELL VACCINATION IN CONJUNCTION WITH ADJUVANT TLR-3 AGONIST ADMINISTRATION ENHANCES PRO-INFLAMMATORY IMMUNE RESPONSES AND IS ASSOCIATED WITH EXTENDED SURVIVAL IN MALIGNANT GLIOMA PATIENTS
Chavez C, Everson R, Orpilla J, Lee A, Khattab S, Antonios J, Salazar A, Cloughesy T, Liau L, Sun L, Hugo W, Prins R. CTIM-18. DENDRITIC CELL VACCINATION IN CONJUNCTION WITH ADJUVANT TLR-3 AGONIST ADMINISTRATION ENHANCES PRO-INFLAMMATORY IMMUNE RESPONSES AND IS ASSOCIATED WITH EXTENDED SURVIVAL IN MALIGNANT GLIOMA PATIENTS. Neuro-Oncology 2020, 22: ii36-ii37. PMCID: PMC7650313, DOI: 10.1093/neuonc/noaa215.152.Peer-Reviewed Original ResearchPatient's peripheral blood mononuclear cellsMalignant glioma patientsToll-like receptorsImmune responsePoly ICLCDendritic cellsClinical trialsTumor lysate-pulsed DCGlioma patientsTLR-3Lysate-pulsed DCPeripheral blood mononuclear cellsPhase II clinical trialTLR-7 agonistDendritic cell vaccinesPro-inflammatory immune responseWHO grade IIITLR-3 agonistIncreased expression of pro-inflammatory genesMGMT methylation statusBlood mononuclear cellsII clinical trialsExpression of pro-inflammatory genesPro-inflammatory responseExpression of pro-inflammatory factors
2017
Modeling neuro-immune interactions during Zika virus infection
Mesci P, Macia A, LaRock CN, Tejwani L, Fernandes IR, Suarez NA, de A. Zanotto PM, Beltrão-Braga PCB, Nizet V, Muotri AR. Modeling neuro-immune interactions during Zika virus infection. Human Molecular Genetics 2017, 27: 41-52. PMID: 29048558, PMCID: PMC5886060, DOI: 10.1093/hmg/ddx382.Peer-Reviewed Original ResearchConceptsNeuro-immune interactionsZika virus infectionVirus infectionSerious neurologic complicationsAntiviral immune responsePro-inflammatory responseSimilar pro-inflammatory responsesNeural precursor cellsNew therapeutic drugsZIKV pathologyHepatitis CNeurologic complicationsMicroglia interactionsHuman microgliaImmune responseViral infectionBrazilian ZIKVMicrogliaInfectionNeural cellsTherapeutic drugsBirth defectsPrecursor cellsDrugsHuman tissues
2016
Host Resistance and Immune Aging
Bandaranayake T, Shaw AC. Host Resistance and Immune Aging. Clinics In Geriatric Medicine 2016, 32: 415-432. PMID: 27394014, PMCID: PMC6986475, DOI: 10.1016/j.cger.2016.02.007.Peer-Reviewed Original ResearchConceptsImmune systemImpaired innate immune responseToll-like receptor functionEarly pro-inflammatory responseNeutrophil extracellular trap formationT cell compartmentB cell subsetsPro-inflammatory responseExtracellular trap formationInnate immune responseInnate immune systemAdaptive immune systemHuman immune systemBasal inflammationCytomegalovirus infectionImmune agingCell subsetsImmunologic challengeImmune responseT-lineageReceptor functionOlder adultsFunction altersCell compartmentAgeDiacylglycerol lipase β inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain
Wilkerson J, Ghosh S, Bagdas D, Mason B, Crowe M, Hsu K, Wise L, Kinsey S, Damaj M, Cravatt B, Lichtman A. Diacylglycerol lipase β inhibition reverses nociceptive behaviour in mouse models of inflammatory and neuropathic pain. British Journal Of Pharmacology 2016, 173: 1678-1692. PMID: 26915789, PMCID: PMC4842918, DOI: 10.1111/bph.13469.Peer-Reviewed Original ResearchConceptsChronic constrictive injuryNeuropathic pain modelWild-type miceAllodynic responsesInflammatory painPain modelLPS modelSide effectsExpression of LPSDiscernible side effectsUntoward side effectsPro-inflammatory responseEvidence of toleranceSites of inflammationConstrictive injuryMechanical allodyniaIntraplantar injectionNeuropathic painPathological painInflammatory mediatorsMouse peritoneal macrophagesLocus of actionNociceptive behaviorSciatic nerveAllodynia
2013
Endocytosis of Mycobacterium tuberculosis Heat Shock Protein 60 Is Required to Induce Interleukin-10 Production in Macrophages*
Parveen N, Varman R, Nair S, Das G, Ghosh S, Mukhopadhyay S. Endocytosis of Mycobacterium tuberculosis Heat Shock Protein 60 Is Required to Induce Interleukin-10 Production in Macrophages*. Journal Of Biological Chemistry 2013, 288: 24956-24971. PMID: 23846686, PMCID: PMC3750191, DOI: 10.1074/jbc.m113.461004.Peer-Reviewed Original ResearchConceptsToll-like receptorsIL-10 productionPro-inflammatory responseHeat shock protein 60Shock protein 60Immune responseInnate responseHost protective immune responsesProtein 60Interleukin-10 productionType immune responseProtective immune responseProduction of interleukinAnti-tuberculosis immunityTumor necrosis factorInnate immune responseMacrophage innate responsesMycobacterium tuberculosis bacteriaTLR4 receptorNecrosis factorP38 MAPK activationTLR2M. tuberculosisTuberculosis bacteriaP38 MAPK
2008
Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety
Yang X, Izadi H, Coleman AS, Wang P, Ma Y, Fikrig E, Anguita J, Pal U. Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety. Microbes And Infection 2008, 10: 1300-1308. PMID: 18725314, PMCID: PMC2648844, DOI: 10.1016/j.micinf.2008.07.029.Peer-Reviewed Original ResearchConceptsB mutantsWild-type B. burgdorferiP38 MAP kinase pathwayMAP kinase pathwayHuman synovial cellsSynovial cellsProtein moietyP38 MAP kinaseNF-kappaBLyme arthritisB operonKinase pathwayMAP kinaseRecombinant BmpAPro-inflammatory cytokines TNF-alphaCultured human synovial cellsLipopolysaccharide inhibitorMutantsCytokines TNF-alphaHost inflammatory responsePro-inflammatory responseCytokine responsesIL-1betaTNF-alphaInflammatory response
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