2023
Metabolomic changes associated with acquired resistance to Ixodes scapularis
Cui Y, Matias J, Tang X, Cibichakravarthy B, DePonte K, Wu M, Fikrig E. Metabolomic changes associated with acquired resistance to Ixodes scapularis. Ticks And Tick-borne Diseases 2023, 15: 102279. PMID: 37972499, DOI: 10.1016/j.ttbdis.2023.102279.Peer-Reviewed Original ResearchGuinea pigsHydroxyphenyllactic acidMetabolome of serumGroups of miceTyrosine metabolic pathwayTick biteImmune responseControl animalsIxodes scapularisTick salivaI. scapularisMiceInduction of componentsMetabolomic changesMortalityNitisinoneMolecular mechanismsAnimalsMetabolism pathwaysTyrosine degradationPigsTyrosine metabolism pathwayMetabolic pathwaysScapularisMetabolomeA mosquito AgTRIO mRNA vaccine contributes to immunity against malaria
Chuang Y, Alameh M, Abouneameh S, Raduwan H, Ledizet M, Weissman D, Fikrig E. A mosquito AgTRIO mRNA vaccine contributes to immunity against malaria. Npj Vaccines 2023, 8: 88. PMID: 37286568, PMCID: PMC10244833, DOI: 10.1038/s41541-023-00679-x.Peer-Reviewed Original ResearchHumoral responseFuture malaria vaccinesMosquito saliva proteinsRobust humoral responseImmunization of miceVector antigensIsotype antibodiesIgG titersImmunized miceMalaria vaccinePassive immunizationIgG2a isotypesMRNA vaccinesPlasmodium infectionMosquito bitesMRNA lipid nanoparticlesVaccineMRNA-LNPPlasmodium sporozoitesMalariaMiceImmunizationSaliva proteinsPotential usefulnessVertebrate hosts
2022
Erratum to “AgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection” [Vaccine 39(12) (2021) 1675–1679]
Marin-Lopez A, Wang Y, Jiang J, Ledizet M, Fikrig E. Erratum to “AgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection” [Vaccine 39(12) (2021) 1675–1679]. Vaccine 2022, 40: 5404-5405. PMID: 35907678, DOI: 10.1016/j.vaccine.2022.05.024.Peer-Reviewed Original Research
2021
A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice
Chuang YM, Tang XD, Fikrig E. A Mosquito AgTRIO Monoclonal Antibody Reduces Early Plasmodium Infection of Mice. Infection And Immunity 2021, 90: e00359-21. PMID: 34724388, PMCID: PMC8788779, DOI: 10.1128/iai.00359-21.Peer-Reviewed Original ResearchConceptsMonoclonal antibodiesFuture malaria vaccinesInfection of miceIsotype monoclonal antibodyVector antigensProtective immunityPassive immunizationMalaria vaccinePlasmodium infectionPassive transferProtein monoclonal antibodySignificant protectionSynergistic protectionMiceInfectionAntibodiesFc regionAntiserumVertebrate hostsProtein TrioImmunizationVaccineMalariaAntigenImmunityAgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection
Marin-Lopez A, Wang Y, Jiang J, Ledizet M, Fikrig E. AgBR1 and NeSt1 antisera protect mice from Aedes aegypti-borne Zika infection. Vaccine 2021, 39: 1675-1679. PMID: 33622591, PMCID: PMC7990057, DOI: 10.1016/j.vaccine.2021.01.072.Peer-Reviewed Original ResearchConceptsMosquito saliva proteinsPassive immunizationZIKV infectionEarly host responseDiverse clinical symptomsViral burdenSaliva proteinsClinical symptomsVaccine strategiesZika infectionHost responseModel antigenInfectionPartial protectionMiceImmunizationZIKVAntiserumIndividual antiseraAgBR1ViremiaSymptomsAntigenBloodAntibodies
2020
The Effects of A Mosquito Salivary Protein on Sporozoite Traversal of Host Cells
Chuang YM, Agunbiade TA, Tang XD, Freudzon M, Almeras L, Fikrig E. The Effects of A Mosquito Salivary Protein on Sporozoite Traversal of Host Cells. The Journal Of Infectious Diseases 2020, 224: 544-553. PMID: 33306099, PMCID: PMC8328219, DOI: 10.1093/infdis/jiaa759.Peer-Reviewed Original ResearchConceptsPassive immunizationCell traversal activityMosquito saliva proteinsMosquito salivary proteinsMosquito salivaNeutrophil chemotaxisProtein monoclonal antibodyProtective effectSporozoite glidingSporozoite infectivitySporozoite traversalMonoclonal antibodiesHost skinAnopheles mosquitoesProtein 1ImmunizationBlood mealSporozoitesSalivaMiceHost cellsSaliva proteinsSalivary proteinsAntiserumVertebrate hostsAn Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector
Cao Y, Rosen C, Arora G, Gupta A, Booth CJ, Murfin KE, Cerny J, Lopez A, Chuang YM, Tang X, Pal U, Ring A, Narasimhan S, Fikrig E. An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector. Infection And Immunity 2020, 88: 10.1128/iai.00426-20. PMID: 32928964, PMCID: PMC7671890, DOI: 10.1128/iai.00426-20.Peer-Reviewed Original ResearchConceptsTick gutTick bite siteVector-host interfaceAbility of spirochetesProtein disulfide isomerase A3Infected vertebrate hostsInflammatory responseBite siteLyme diseaseVertebrate hostsGutTick proteinsAdditional targetsMiceSpirochete life cycleSpirochete survivalArthropod vectorsSpirochetesRNA interferenceIllnessTicksMacrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice
Yang L, Geng T, Yang G, Ma J, Wang L, Ketkar H, Yang D, Lin T, Hwang J, Zhu S, Wang Y, Dai J, You F, Cheng G, Vella AT, Flavell RA, Fikrig E, Wang P. Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice. Communications Biology 2020, 3: 556. PMID: 33033362, PMCID: PMC7545163, DOI: 10.1038/s42003-020-01285-6.Peer-Reviewed Original ResearchConceptsMacrophage scavenger receptor 1Scavenger receptor 1Chikungunya virusReceptor 1Antiviral roleType I IFN responseChikungunya virus infectionLow-density lipoproteinImportant antiviral roleI IFN responseMarkers of autophagyCHIKV infectionViral loadArthritogenic alphavirusesVirus infectionCHIKV replicationATG5-ATG12Antiviral actionKnockout miceMSR1 expressionIFN responseInfectionMiceNsp1 proteinAutophagic functionRepeat tick exposure elicits distinct immune responses in guinea pigs and mice
Kurokawa C, Narasimhan S, Vidyarthi A, Booth CJ, Mehta S, Meister L, Diktas H, Strank N, Lynn GE, DePonte K, Craft J, Fikrig E. Repeat tick exposure elicits distinct immune responses in guinea pigs and mice. Ticks And Tick-borne Diseases 2020, 11: 101529. PMID: 32993942, PMCID: PMC7530331, DOI: 10.1016/j.ttbdis.2020.101529.Peer-Reviewed Original ResearchConceptsGuinea pigsElicit distinct immune responsesDistinct immune responsesGuinea pig modelLocal blood flowImmune animalsInflammatory pathwaysTick rejectionMechanisms of resistanceImmune responseMouse modelVaccine candidatesBite siteBlood flowPig modelCoagulation pathwayComplement activationAcquired ResistanceProtective antigenTick detachmentTick proteinsBlood mealMiceTick infestationRNA sequencingVaccination with Aedes aegypti AgBR1 Delays Lethal Mosquito-Borne Zika Virus Infection in Mice
Wang Y, Marin-Lopez A, Jiang J, Ledizet M, Fikrig E. Vaccination with Aedes aegypti AgBR1 Delays Lethal Mosquito-Borne Zika Virus Infection in Mice. Vaccines 2020, 8: 145. PMID: 32218189, PMCID: PMC7348886, DOI: 10.3390/vaccines8020145.Peer-Reviewed Original ResearchZika virusZIKV infectionGuillain-Barre syndromeMosquito salivary proteinsZika virus infectionNeurological complicationsAcute illnessFetal microcephalyPassive immunizationActive immunizationAsymptomatic infectionInflammatory responseAedes aegypti mosquitoesVirus infectionBite siteInfectionAegypti mosquitoesImmunizationMiceSalivary proteinsAgBR1MosquitoesComplicationsHeadacheVaccination
2019
Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice
Chuang YM, Freudzon M, Yang J, Dong Y, Dimopoulos G, Fikrig E. Anopheles gambiae Lacking AgTRIO Inefficiently Transmits Plasmodium berghei to Mice. Infection And Immunity 2019, 87: 10.1128/iai.00326-19. PMID: 31285253, PMCID: PMC6704594, DOI: 10.1128/iai.00326-19.Peer-Reviewed Original ResearchConceptsBite siteControl mosquitoesMosquito salivary proteinsInfectivity of sporozoitesMosquito salivary glandsProinflammation cytokinesSporozoite infectionRNA interference-mediated silencingPlasmodium bergheiMiceSalivary glandsSporozoitesTNFExpression of genesMosquitoesSalivary proteinsBurdenExpressionVertebrate hostsSplenocytesCytokinesInfectionCell adhesionLiverBergheiBorrelia miyamotoi infection leads to cross-reactive antibodies to the C6 peptide in mice and men
Koetsveld J, Platonov A, Kuleshov K, Wagemakers A, Hoornstra D, Ang W, Szekeres S, van Duijvendijk G, Fikrig E, Embers M, Sprong H, Hovius J. Borrelia miyamotoi infection leads to cross-reactive antibodies to the C6 peptide in mice and men. Clinical Microbiology And Infection 2019, 26: 513.e1-513.e6. PMID: 31404672, DOI: 10.1016/j.cmi.2019.07.026.Peer-Reviewed Original ResearchConceptsCross-reactive antibodiesC6 peptideEnzyme immunoassayLyme borreliosisBorrelia miyamotoi infectionBMD patientsExperimental murine infectionC6 enzyme immunoassayAvailable immunoblotNegative immunoblotMiyamotoi infectionTick bitePatient seraMurine infectionPatientsReactivity testingInfectionVlsE proteinBorrelia miyamotoiBorrelia burgdorferiMiceAgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice
Uraki R, Hastings AK, Brackney DE, Armstrong PM, Fikrig E. AgBR1 antibodies delay lethal Aedes aegypti-borne West Nile virus infection in mice. Npj Vaccines 2019, 4: 23. PMID: 31312526, PMCID: PMC6614468, DOI: 10.1038/s41541-019-0120-x.Peer-Reviewed Original ResearchWest Nile virus infectionWest Nile virusVirus infectionInfected Aedes aegypti mosquitoesZika virus pathogenesisMosquito salivary proteinsViral loadAedes aegypti mosquitoesLethal infectionVirus pathogenesisSevere diseaseInfectionNile virusAegypti mosquitoesMiceAntibodiesSalivary proteinsMosquitoesMeningoencephalitisPathogenesisAgBR1DiseaseELF4 facilitates innate host defenses against Plasmodium by activating transcription of Pf4 and Ppbp
Wang D, Zhang Z, Cui S, Zhao Y, Craft S, Fikrig E, You F. ELF4 facilitates innate host defenses against Plasmodium by activating transcription of Pf4 and Ppbp. Journal Of Biological Chemistry 2019, 294: 7787-7796. PMID: 30898878, PMCID: PMC6514618, DOI: 10.1074/jbc.ra118.006321.Peer-Reviewed Original ResearchConceptsPlatelet factor 4Host defenseComponent of plateletsPro-platelet basic proteinKilling of parasitesFactor 4Innate immune moleculesInnate immune signalingInnate host defenseC chemokinesWT littermatesTranscription factor 4Control animalsImmune moleculesInnate immunityInfected erythrocytesImmune signalingInfectionExpression levelsMiceType IBasic proteinDefense peptidesPlateletsPlasmodiumAedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserumLoss of the TAM Receptor Axl Ameliorates Severe Zika Virus Pathogenesis and Reduces Apoptosis in Microglia
Hastings AK, Hastings K, Uraki R, Hwang J, Gaitsch H, Dhaliwal K, Williamson E, Fikrig E. Loss of the TAM Receptor Axl Ameliorates Severe Zika Virus Pathogenesis and Reduces Apoptosis in Microglia. IScience 2019, 13: 339-350. PMID: 30884311, PMCID: PMC6424058, DOI: 10.1016/j.isci.2019.03.003.Peer-Reviewed Original ResearchZIKV infectionZIKV pathogenesisVirus infectionAxl-deficient miceZika virus pathogenesisRole of AxlZika virus infectionAlpha/beta receptorTAM receptor AxlInterferon alpha/beta receptorTAM receptorsVirus pathogenesisMouse modelEntry receptorBeta receptorsReceptor AxlViral infectionAXL inhibitorAxl receptorInfectionPathogenesisAxlMiceLess apoptosisReceptorsModeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor
Marín-Lopez A, Calvo-Pinilla E, Moreno S, Utrilla-Trigo S, Nogales A, Brun A, Fikrig E, Ortego J. Modeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor. Viruses 2019, 11: 35. PMID: 30625992, PMCID: PMC6356211, DOI: 10.3390/v11010035.Peer-Reviewed Original ResearchConceptsMouse modelAnimal modelsArbovirus infectionInterferon α/β receptorAlpha/beta receptorAppropriate animal modelsNatural hostInterferon alpha/beta receptorSafe therapyProtective efficacyArboviral infectionsImmune responseAdult miceBeta receptorsNew vaccinesDisease pathogenesisExtrapolation of findingsΒ receptorExperimental infectionBiosafety level 3MiceInfectionStatistical significanceVirusPathogenesis
2018
Circadian Rhythms Influence the Severity of Sepsis in Mice via a TLR2-Dependent, Leukocyte-Intrinsic Mechanism
Heipertz EL, Harper J, Lopez CA, Fikrig E, Hughes ME, Walker WE. Circadian Rhythms Influence the Severity of Sepsis in Mice via a TLR2-Dependent, Leukocyte-Intrinsic Mechanism. The Journal Of Immunology 2018, 201: ji1701677. PMID: 29760192, PMCID: PMC9351006, DOI: 10.4049/jimmunol.1701677.Peer-Reviewed Original ResearchConceptsImmune cellsZT 19C57BL/6 miceWorse outcomesTLR2 agonist lipoteichoic acidCircadian rhythmTLR2 knockout miceFemale C57BL/6 miceMale C57BL/6 miceSeverity of sepsisBone marrow chimerasTLR2-dependent mechanismIL-6 productionTLR2-DependentSepsis severityCecal ligationSepsis phenotypesSepsisC57BL/6 cellsSimilar outcomesMiceMouse cecumLipoteichoic acidMurine macrophagesCLPUBXN3B positively regulates STING-mediated antiviral immune responses
Yang L, Wang L, Ketkar H, Ma J, Yang G, Cui S, Geng T, Mordue DG, Fujimoto T, Cheng G, You F, Lin R, Fikrig E, Wang P. UBXN3B positively regulates STING-mediated antiviral immune responses. Nature Communications 2018, 9: 2329. PMID: 29899553, PMCID: PMC5998066, DOI: 10.1038/s41467-018-04759-8.Peer-Reviewed Original ResearchConceptsUbiquitin regulatory X domain-containing proteinAntiviral immune responseImmune responseDeficient immune responseDomain-containing proteinsInterferon genes (STING) signalingVesicular stomatitis virus infectionDiverse biological processesStomatitis virus infectionPhosphorylation of TBK1Physiological evidenceHerpes simplex virus 1Cre-loxP approachSimplex virus 1Virus infectionAdult miceGene signalingHSV-1Biological processesPhysiological functionsVirus 1MicePrimary cellsConsequent recruitmentResponseImmunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice
Dragovic SM, Agunbiade TA, Freudzon M, Yang J, Hastings AK, Schleicher TR, Zhou X, Craft S, Chuang YM, Gonzalez F, Li Y, Hrebikova G, Tripathi A, Mlambo G, Almeras L, Ploss A, Dimopoulos G, Fikrig E. Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice. Cell Host & Microbe 2018, 23: 523-535.e5. PMID: 29649443, PMCID: PMC5998332, DOI: 10.1016/j.chom.2018.03.008.Peer-Reviewed Original ResearchConceptsPlasmodium infectionBerghei infectionMosquito salivary gland antigensPlasmodium berghei infectionPlasmodium circumsporozoite proteinSalivary gland antigensAnopheles salivaHumanized miceActive immunizationLiver burdenVaccine candidatesInfected mosquitoesCircumsporozoite proteinHost responseMurine dermisInfectionPlasmodium falciparumMiceSalivary glandsSaliva componentsImmunizationAnopheline mosquitoesMalariaAntiserumAntibodies