2024
mRNA vaccination of rabbits alters the fecundity, but not the attachment, of adult Ixodes scapularis
Matias J, Cui Y, Lynn G, DePonte K, Mesquita E, Muramatsu H, Alameh M, Dwivedi G, Tam Y, Pardi N, Weissman D, Fikrig E. mRNA vaccination of rabbits alters the fecundity, but not the attachment, of adult Ixodes scapularis. Scientific Reports 2024, 14: 496. PMID: 38177212, PMCID: PMC10766947, DOI: 10.1038/s41598-023-50389-6.Peer-Reviewed Original Research
2023
Specific mRNA lipid nanoparticles and acquired resistance to ticks
Matias J, Cui Y, Tang X, Sajid A, Arora G, Wu M, DePonte K, Muramatsu H, Tam Y, Narasimhan S, Pardi N, Weissman D, Fikrig E. Specific mRNA lipid nanoparticles and acquired resistance to ticks. Vaccine 2023, 41: 4996-5002. PMID: 37407406, PMCID: PMC10530371, DOI: 10.1016/j.vaccine.2023.06.081.Peer-Reviewed Original Research
2021
Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies
Matias J, Kurokawa C, Sajid A, Narasimhan S, Arora G, Diktas H, Lynn GE, DePonte K, Pardi N, Valenzuela JG, Weissman D, Fikrig E. Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies. Vaccine 2021, 39: 7661-7668. PMID: 34862075, PMCID: PMC8671329, DOI: 10.1016/j.vaccine.2021.11.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNAGuinea PigsIxodesLiposomesNanoparticlesRNA, MessengerSalivary Proteins and PeptidesVaccinesConceptsTick bite siteTick immunityAntigen deliveryBite siteGuinea pigsDevelopment of vaccinesIxodes scapularis ticksProtein immunizationAntibody responseTick biteVaccine platformLipid nanoparticlesMRNA lipid nanoparticlesMRNA-LNPModel antigenTick salivaEarly hallmarkImmunityTick-borne diseasesScapularis ticksTick challengeErythemaSalivary componentsFactor XaDelivery strategiesmRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent
Sajid A, Matias J, Arora G, Kurokawa C, DePonte K, Tang X, Lynn G, Wu MJ, Pal U, Strank NO, Pardi N, Narasimhan S, Weissman D, Fikrig E. mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Science Translational Medicine 2021, 13: eabj9827. PMID: 34788080, DOI: 10.1126/scitranslmed.abj9827.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGuinea PigsIxodesLiposomesLyme DiseaseMRNA VaccinesNanoparticlesRNA, MessengerVaccinationVaccines, SyntheticConceptsTick-borne infectionsTick-borne infectious diseaseEngorgement weightDisease agentsTicksTick exposureLyme disease agentGuinea pigsTick biteNormal blood mealBlood mealNucleoside-modified mRNALyme diseasePigsLocal rednessMRNA vaccinationMRNA vaccinesBite siteSalivary proteinsPrevents transmissionInfectious diseasesDiseaseVaccineResistanceEffective induction
2015
Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers
Walker WE, Kurscheid S, Joshi S, Lopez CA, Goh G, Choi M, Barakat L, Francis J, Fisher A, Kozal M, Zapata H, Shaw A, Lifton R, Sutton RE, Fikrig E. Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers. Journal Of Virology 2015, 89: 5502-5514. PMID: 25740989, PMCID: PMC4442529, DOI: 10.1128/jvi.00118-15.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCase-Control StudiesCD4-Positive T-LymphocytesChemokine CCL3Chemokine CCL4Chemokine CCL5Chemokines, CCCohort StudiesFemaleGene DosageHIV InfectionsHIV Long-Term SurvivorsHIV-1Host-Pathogen InteractionsHumansMacrophage Inflammatory ProteinsMaleMiddle AgedReceptors, CCR5Receptors, CXCR4RNA, MessengerUp-RegulationConceptsElite controllersHIV-seropositive individualsAntiretroviral therapyT cellsMIP-1βMIP-1αHIV infectionSeropositive individualsAbsence of ARTR5-tropic HIV-1Macrophage inflammatory protein-1αR5-tropic HIVInflammatory protein-1αT cell resistancePandemic health problemRANTES chemokinesHIV replicationRare patientsHealthy controlsTherapeutic effectHIV entryHIV-1X4-tropicHealth problemsProtein-1α
2012
Enhanced Survival of Plasmodium-Infected Mosquitoes during Starvation
Zhao YO, Kurscheid S, Zhang Y, Liu L, Zhang L, Loeliger K, Fikrig E. Enhanced Survival of Plasmodium-Infected Mosquitoes during Starvation. PLOS ONE 2012, 7: e40556. PMID: 22808193, PMCID: PMC3393683, DOI: 10.1371/journal.pone.0040556.Peer-Reviewed Original ResearchConceptsSurvival advantageInsulin-like signalingAbility of mosquitoesInsulin-like peptidesInfection altersUninfected mosquitoesOocyst developmentPlasmodium developmentEnhanced expressionInsect vectorsPeriods of starvationFitness costsEnhanced survivalVertebrate hostsMicroarray analysisCarbohydrate catabolismCause malariaPlasmodiumStarvationMosquitoes
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 mechanismAn In Vivo Transfection Approach Elucidates a Role for Aedes aegypti Thioester-Containing Proteins in Flaviviral Infection
Cheng G, Liu L, Wang P, Zhang Y, Zhao YO, Colpitts TM, Feitosa F, Anderson JF, Fikrig E. An In Vivo Transfection Approach Elucidates a Role for Aedes aegypti Thioester-Containing Proteins in Flaviviral Infection. PLOS ONE 2011, 6: e22786. PMID: 21818390, PMCID: PMC3144946, DOI: 10.1371/journal.pone.0022786.Peer-Reviewed Original Research
2010
Tick Histamine Release Factor Is Critical for Ixodes scapularis Engorgement and Transmission of the Lyme Disease Agent
Dai J, Narasimhan S, Zhang L, Liu L, Wang P, Fikrig E. Tick Histamine Release Factor Is Critical for Ixodes scapularis Engorgement and Transmission of the Lyme Disease Agent. PLOS Pathogens 2010, 6: e1001205. PMID: 21124826, PMCID: PMC2991271, DOI: 10.1371/journal.ppat.1001205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorBlotting, WesternBorrelia burgdorferiFeeding BehaviorFemaleHistamineHumansImmunizationIxodesLyme DiseaseMiceMice, Inbred C3HReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSalivaTick InfestationsTumor Protein, Translationally-Controlled 1ConceptsTick-borne pathogensB. burgdorferi transmissionTick engorgementB. burgdorferi burdenHistamine-releasing factorRapid feeding phaseBurgdorferi-infected ticksAnimal healthTick feedingTick salivaDiverse infectious agentsDisease agentsTicksIxodes scapularisLyme disease agentRNA interferenceFeeding phaseVaccine potentialQuantitative reverse transcription PCRReverse transcription-PCRHistamine releaseEffective vaccineVascular permeabilityBlood flowInfectious agents
2008
Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization
Hovius JW, de Jong MA, Dunnen J, Litjens M, Fikrig E, van der Poll T, Gringhuis SI, Geijtenbeek TB. Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization. PLOS Pathogens 2008, 4: e31. PMID: 18282094, PMCID: PMC2242833, DOI: 10.1371/journal.ppat.0040031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiCell Adhesion MoleculesCells, CulturedCytokinesDendritic CellsDose-Response Relationship, DrugHumansIxodesLectins, C-TypeNucleosomesProtein BindingProto-Oncogene Proteins c-rafReceptors, Cell SurfaceRecombinant ProteinsRNA, MessengerSalivary Proteins and PeptidesToll-Like ReceptorsConceptsRaf-1B. burgdorferi infectionSerine/threonine kinase Raf-1Mitogen-activated protein kinase kinaseKinase Raf-1Post-transcriptional levelLyme diseaseProtein kinase kinaseRaf-1 activationBurgdorferi infectionDC-SIGNTNF-alpha mRNA stabilityHuman dendritic cell functionNucleosome remodelingTick salivary proteinsDendritic cell functionKinase kinasePro-inflammatory cytokinesAdaptive immune responsesToll-like receptorsMRNA stabilityMRNA stabilizationT cell activationMolecular mechanismsMajor vector
2007
A Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector
Narasimhan S, Sukumaran B, Bozdogan U, Thomas V, Liang X, DePonte K, Marcantonio N, Koski RA, Anderson JF, Kantor F, Fikrig E. A Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector. Cell Host & Microbe 2007, 2: 7-18. PMID: 18005713, PMCID: PMC2699493, DOI: 10.1016/j.chom.2007.06.001.Peer-Reviewed Original ResearchConceptsMammalian hostsComplex feeding sitesLyme disease agent Borrelia burgdorferiSuccessful migrationMammalian responseTick Ixodes scapularisTick salivary glandsReactive oxygen speciesFeeding sitesArthropod vectorsTick proteinsBurgdorferi-infected miceOxygen speciesEfficient vectorCritical roleSpirochete acquisitionIxodes scapularisB. burgdorferiPathogensHostBorrelia burgdorferiI. scapularisInflammatory cellsImmune cellsSurvival advantage
2005
Effects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels
Carlyon JA, Ryan D, Archer K, Fikrig E. Effects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels. Infection And Immunity 2005, 73: 7629-7636. PMID: 16239567, PMCID: PMC1273867, DOI: 10.1128/iai.73.11.7629-7636.2005.Peer-Reviewed Original ResearchConceptsFerritin protein levelsProtein levelsHL-60 cellsA. phagocytophilumAnaplasma phagocytophilumSerum-opsonized zymosanHuman granulocytic anaplasmosisA. phagocytophilum infectionInfected HL-60 cellsTime-dependent mannerObligate intracellular bacteriumFerritin levelsInfected miceA. phagocytophilum-infected miceMajor intracellular iron storage proteinFerritin heavy chainHuman promyelocytic HL-60 cellsNADPH oxidase assemblyNeutrophilsPromyelocytic HL-60 cellsMRNA expressionPhagocytophilum infectionIntracellular pathogensGranulocytic anaplasmosisIntracellular bacteriumThe Lyme disease agent exploits a tick protein to infect the mammalian host
Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, Anguita J, Norgard MV, Kantor FS, Anderson JF, Koski RA, Fikrig E. The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 2005, 436: 573-577. PMID: 16049492, PMCID: PMC4306560, DOI: 10.1038/nature03812.Peer-Reviewed Original Research
2004
Borrelia burgdorferi outer surface protein (osp) B expression independent of ospA
Liang FT, Caimano MJ, Radolf JD, Fikrig E. Borrelia burgdorferi outer surface protein (osp) B expression independent of ospA. Microbial Pathogenesis 2004, 37: 35-40. PMID: 15194158, DOI: 10.1016/j.micpath.2004.02.007.Peer-Reviewed Original ResearchAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiDisease Models, AnimalGene Expression Regulation, BacterialLipoproteinsLyme DiseaseMiceMice, Inbred BALB CMice, SCIDPromoter Regions, GeneticRNA, BacterialRNA, MessengerTicksTranscription, Genetic
2002
Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation
Carlyon JA, Chan WT, Galán J, Roos D, Fikrig E. Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation. The Journal Of Immunology 2002, 169: 7009-7018. PMID: 12471136, DOI: 10.4049/jimmunol.169.12.7009.Peer-Reviewed Original ResearchConceptsInfected HL-60 cellsHL-60 cellsAnaplasma phagocytophilaMRNA expressionNADPH oxidaseRetinoic acid-differentiated HL-60 cellsBacterial intracellular survivalHuman granulocytic ehrlichiosisNADPH oxidase activityNADPH oxidase activationQuantitative RT-PCRCMV immediate-early promoterInfected neutrophilsEtiologic agentGranulocytic ehrlichiosisRT-PCR analysisA. phagocytophilaIntracellular survivalSuperoxide productionOxidase activationNeutrophilsProtein expressionRT-PCRImmediate early promoterH postinfectionExamination of the Borrelia burgdorferi Transcriptome in Ixodes scapularis during Feeding
Narasimhan S, Santiago F, Koski RA, Brei B, Anderson JF, Fish D, Fikrig E. Examination of the Borrelia burgdorferi Transcriptome in Ixodes scapularis during Feeding. Journal Of Bacteriology 2002, 184: 3122-3125. PMID: 12003955, PMCID: PMC135063, DOI: 10.1128/jb.184.11.3122-3125.2002.Peer-Reviewed Original ResearchConceptsBorrelia burgdorferi gene expressionB. burgdorferi genesPeriplasmic proteinsSignal transductionChromosomal genesPutative lipoproteinSubstrate transportGene expressionDifferential expressionGenesEnergy metabolismIxodes scapularis ticksGlobal analysisIxodes scapularisScapularis ticksExpressionTranscriptomeTransductionTicksProteinFeedingMetabolismScapularis
2001
Salp25D, an Ixodes scapularis Antioxidant, Is 1 of 14 Immunodominant Antigens in Engorged Tick Salivary Glands
Das S, Banerjee G, DePonte K, Marcantonio N, Kantor F, Fikrig E. Salp25D, an Ixodes scapularis Antioxidant, Is 1 of 14 Immunodominant Antigens in Engorged Tick Salivary Glands. The Journal Of Infectious Diseases 2001, 184: 1056-1064. PMID: 11574922, DOI: 10.1086/323351.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsAntigensAntioxidantsCattleCloning, MolecularConsensus SequenceEnzyme-Linked Immunosorbent AssayFemaleGene LibraryGlutathione PeroxidaseGuinea PigsHumansImmunoglobulin GInsect ProteinsIxodesMiceMice, Inbred C3HMolecular Sequence DataNematodaRabbitsRNA, MessengerSalivary GlandsSequence Homology, Amino AcidSpecies SpecificityTime Factors
2000
Arthropod- and Host-Specific Borrelia burgdorferi bbk32 Expression and the Inhibition of Spirochete Transmission
Fikrig E, Feng W, Barthold S, Telford S, Flavell R. Arthropod- and Host-Specific Borrelia burgdorferi bbk32 Expression and the Inhibition of Spirochete Transmission. The Journal Of Immunology 2000, 164: 5344-5351. PMID: 10799897, DOI: 10.4049/jimmunol.164.10.5344.Peer-Reviewed Original ResearchConceptsSpirochete transmissionLyme borreliosisB. burgdorferi infectionB. burgdorferi transmissionMechanisms of immunityIxodes scapularis ticksCutaneous sitesImmunized miceSpirochete numbersBurgdorferi infectionMurine infectionMurine hostMiceInfectionMRNA levelsScapularis ticksB. burgdorferiTick engorgementMurine tissuesVector-borne diseasesBorreliosisAdult ticksAntiserumBBK32Regulated expressionCutting Edge: Infection by the Agent of Human Granulocytic Ehrlichiosis Prevents the Respiratory Burst by Down-Regulating gp91phox
Banerjee R, Anguita J, Roos D, Fikrig E. Cutting Edge: Infection by the Agent of Human Granulocytic Ehrlichiosis Prevents the Respiratory Burst by Down-Regulating gp91phox. The Journal Of Immunology 2000, 164: 3946-3949. PMID: 10754283, DOI: 10.4049/jimmunol.164.8.3946.Peer-Reviewed Original ResearchConceptsHGE bacteriaNADPH oxidase enzyme complexHL-60 cellsNADPH oxidaseHuman granulocytic ehrlichiosisEnzyme complexPromyelocytic cell lineTick-borne pathogensInfected cellsCell linesOrganismsMRNA levelsGp91phox proteinRT-PCRDirect inhibitionBacteriaFACS analysisPathogensMRNA expressionOxidaseGenerate superoxide anionCellsRespiratory burstSplenic neutrophilsMicrobes
1999
Selective Anti-Inflammatory Action of Interleukin-11 in Murine Lyme Disease: Arthritis Decreases while Carditis Persists
Anguita J, Barthold S, Samanta S, Ryan J, Fikrig E. Selective Anti-Inflammatory Action of Interleukin-11 in Murine Lyme Disease: Arthritis Decreases while Carditis Persists. The Journal Of Infectious Diseases 1999, 179: 734-737. PMID: 9952389, DOI: 10.1086/314613.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAnti-Inflammatory AgentsArthritis, InfectiousFemaleHumansInflammationInterferon-gammaInterleukin-11Interleukin-12Interleukin-4Lyme DiseaseMiceMice, Inbred C3HMyocarditisNitric Oxide SynthaseNitric Oxide Synthase Type IIRecombinant ProteinsRNA, MessengerTranscription, GeneticConceptsMurine Lyme diseaseIL-11Potent anti-inflammatory propertiesInducible nitric oxide synthaseLyme diseaseMurine Lyme carditisAnti-inflammatory actionRole of interleukinAnti-inflammatory propertiesNitric oxide synthaseInnate immune responseB. burgdorferi-infected miceBurgdorferi-infected miceLyme carditisCardiac inflammationLyme arthritisIL-12Less arthritisIL-4Oxide synthaseBlocking antibodiesImmune responseControl animalsInterleukin-11Borrelia burgdorferi