2024
Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites
Lapidus S, Goheen M, Sy M, Deme A, Ndiaye I, Diedhiou Y, Mbaye A, Hagadorn K, Sene S, Pouye M, Thiam L, Ba A, Guerra N, Mbengue A, Raduwan H, Gagnon J, Vigan-Womas I, Parikh S, Ko A, Ndiaye D, Fikrig E, Chuang Y, Bei A. Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites. The Journal Of Infectious Diseases 2024, jiae525. PMID: 39475423, DOI: 10.1093/infdis/jiae525.Peer-Reviewed Original ResearchModerate transmission areasMosquito salivary proteinsModerately endemic areaAntibody responseMosquito exposureTransmission seasonP. falciparum infectionMalaria transmission seasonMalaria transmission intensityExposure to infectious mosquitoesMosquito bitesEntomological inoculation rateEndemic areasHuman immune responseInfected mosquito bitesTransmission areasDecline 3 monthsNo antibody responseExposure to infected mosquitoesP. falciparumControl cohortExposure to mosquitoesBead-based assayImmune responseSalivary proteins
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 pathwaysScapularisMetabolomeDevelopment of an mRNA-lipid nanoparticle vaccine against Lyme disease
Pine M, Arora G, Hart T, Bettini E, Gaudette B, Muramatsu H, Tombácz I, Kambayashi T, Tam Y, Brisson D, Allman D, Locci M, Weissman D, Fikrig E, Pardi N. Development of an mRNA-lipid nanoparticle vaccine against Lyme disease. Molecular Therapy 2023, 31: 2702-2714. PMID: 37533256, PMCID: PMC10492027, DOI: 10.1016/j.ymthe.2023.07.022.Peer-Reviewed Original ResearchConceptsLyme diseaseImmune responseCell-mediated immune responsesLyme disease vaccinePotent immune responsesProtein subunit vaccinesSARS-CoV-2Surface protein AVector-borne infectious diseasesMRNA-LNP vaccineOuter surface protein ASingle immunizationProtective efficacyMRNA vaccinesClinical vaccinesDisease vaccineNanoparticle vaccineSubunit vaccineVaccine developmentVaccineBacterial infectionsMRNA-LNPInfectious diseasesDiseaseMRNA platformMosquito Salivary Proteins and Arbovirus Infection: From Viral Enhancers to Potential Targets for Vaccines
Marín-López A, Raduwan H, Chen T, Utrilla-Trigo S, Wolfhard D, Fikrig E. Mosquito Salivary Proteins and Arbovirus Infection: From Viral Enhancers to Potential Targets for Vaccines. Pathogens 2023, 12: 371. PMID: 36986293, PMCID: PMC10054260, DOI: 10.3390/pathogens12030371.Peer-Reviewed Original ResearchMosquito salivary proteinsImmune responseImportant public health challengeAdaptive immune responsesHost immune responsePublic health challengeNon-endemic areasSalivary proteinsSerious complicationsLicensed vaccineNeurological alterationsMosquito salivaClinical signsMosquito bitesHemorrhagic feverInfection outcomesRapid onsetArbovirus infectionExplosive outbreaksHealth challengesVaccineDifferent arbovirusesArboviral diseasesArthropod salivaPotential targetRepeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding
Narasimhan S, Booth C, Philipp M, Fikrig E, Embers M. Repeated Tick Infestations Impair Borrelia burgdorferi Transmission in a Non-Human Primate Model of Tick Feeding. Pathogens 2023, 12: 132. PMID: 36678479, PMCID: PMC9861725, DOI: 10.3390/pathogens12010132.Peer-Reviewed Original ResearchNon-human primatesImmune responseLyme diseaseTick transmissionAnimal modelsGuinea pigsNon-human primate modelProtective immune responseTick feedingTick infestationRobust immune responseTick salivary antigensElicit immune responsesHuman Lyme diseaseClinical manifestationsHuman pathogensPrimate modelSalivary antigensNon-natural hostsVaccine targetsDiseaseVaccine discoveryTick resistanceBorreliaNatural host
2022
Aedes aegypti anti-salivary proteins IgG levels in a cohort of DENV-like symptoms subjects from a dengue-endemic region in Colombia
Olajiga O, Marin-Lopez A, Cardenas J, Gutierrez-Silva L, Gonzales-Pabon M, Maldonado-Ruiz L, Worges M, Fikrig E, Park Y, Londono-Renteria B. Aedes aegypti anti-salivary proteins IgG levels in a cohort of DENV-like symptoms subjects from a dengue-endemic region in Colombia. Frontiers In Epidemiology 2022, 2: 1002857. PMID: 38455331, PMCID: PMC10910902, DOI: 10.3389/fepid.2022.1002857.Peer-Reviewed Original ResearchIgG antibodiesDengue virusZika virusWest Nile virus infectionDengue disease progressionSystemic immune responsesPotential protective effectFever endemic areasDengue-endemic regionsSalivary proteinsProduction of antibodiesFemale Aedes mosquitoesSalivary gland extractsNterm-34Clinical characteristicsIgG levelsDENV infectionAntibody responseDisease progressionArboviral infectionsVirus infectionImmune responseMosquito bitesProtective effectImmunomodulatory properties
2020
Acquired tick resistance: The trail is hot
Narasimhan S, Kurokawa C, DeBlasio M, Matias J, Sajid A, Pal U, Lynn G, Fikrig E. Acquired tick resistance: The trail is hot. Parasite Immunology 2020, 43: e12808. PMID: 33187012, PMCID: PMC8058238, DOI: 10.1111/pim.12808.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsA Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus
Geng T, Lin T, Yang D, Harrison AG, Vella AT, Fikrig E, Wang P. A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus. The Journal Of Infectious Diseases 2020, 223: 2186-2196. PMID: 33161431, PMCID: PMC8205639, DOI: 10.1093/infdis/jiaa694.Peer-Reviewed Original ResearchConceptsVirus infectionSTING signalingGt miceType I IFN responseChikungunya virus infectionImmune cell infiltrationWild-type miceActivator of neutrophilsInnate immune responseExpression of interferonI IFN responseExpression of chemoattractantsRNA virus infectionDNA virus infectionInterferon genes (STING) pathwayCHIKV arthritisViremic stageArthritis progressionViral burdenArthritis pathogenesisChemokine responsesCell infiltrationJoint damageImmune responseSTING deficiencyCXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses
Lin T, Geng T, Harrison AG, Yang D, Vella AT, Fikrig E, Wang P. CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses. Viruses 2020, 12: 1252. PMID: 33147869, PMCID: PMC7692144, DOI: 10.3390/v12111252.Peer-Reviewed Original ResearchConceptsChikungunya virusAlphaviral arthritisArthritogenic alphavirusesLargest immune cell populationMacrophages/T cellsImmune cell populationsInflammatory immune responseLow viral loadWild-type miceO'nyong-nyong virusWild-type animalsRheumatic manifestationsImmune infiltratesViral loadT cellsImmune responseAlphaviral diseaseArthritic diseasesTherapeutic targetCXCL10PathogenesisViral RNACell populationsArthritisFootpadRepeat 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 sequencingIxodes scapularis saliva components that elicit responses associated with acquired tick-resistance
Narasimhan S, Kurokawa C, Diktas H, Strank NO, Černý J, Murfin K, Cao Y, Lynn G, Trentleman J, Wu MJ, DePonte K, Kantor F, Anguita J, Hovius J, Fikrig E. Ixodes scapularis saliva components that elicit responses associated with acquired tick-resistance. Ticks And Tick-borne Diseases 2020, 11: 101369. PMID: 31924502, PMCID: PMC7382422, DOI: 10.1016/j.ttbdis.2019.101369.Peer-Reviewed Original ResearchConceptsTick-borne diseasesSalivary antigensAnti-tick vaccine candidatesIxodes scapularisTick salivary antigensTransmission of pathogensTick infestationTick rejectionTick proteinsViable vaccine targetsTick feedingPathogen transmissionRise worldTicksHost immune responseUrgent public health needScapularisMammalian hostsPathogensPublic health needsVaccine candidatesImmune responseSalivary glycoproteinsFeedingVaccine targeting
2019
The role of Mannose Binding Lectin in the immune response against Borrelia burgdorferi sensu lato
Coumou J, Wagemakers A, Narasimhan S, Schuijt TJ, Ersoz JI, Oei A, de Boer OJ, Roelofs JJTH, Fikrig E, Hovius JW. The role of Mannose Binding Lectin in the immune response against Borrelia burgdorferi sensu lato. Scientific Reports 2019, 9: 1431. PMID: 30723261, PMCID: PMC6363739, DOI: 10.1038/s41598-018-37922-8.Peer-Reviewed Original ResearchConceptsMannose-Binding LectinB. burgdorferiImmune responseComplement systemRole of MBLMBL-deficient miceWhole blood stimulationIgG serum antibodiesB. burgdorferi infectionB. burgdorferi numbersHost complement systemMechanism warrants further investigationSerum-sensitive isolatesBorrelia burgdorferi sensu lato groupWarrants further investigationBorrelia burgdorferi sensu latoLater time pointsBinding lectinsSevere courseBlood stimulationDetectable antibodiesBurgdorferi sensu latoSerum antibodiesMBL deficiencyDeficient miceModeling 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 significanceVirusPathogenesis28 Host Defenses to Spirochetes
Navasa N, Fikrig E, Anguita J. 28 Host Defenses to Spirochetes. 2019, 403-411.e1. DOI: 10.1016/b978-0-7020-6896-6.00028-4.Peer-Reviewed Original Research
2018
Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance
Shaw DK, Tate AT, Schneider DS, Levashina EA, Kagan JC, Pal U, Fikrig E, Pedra JHF. Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance. Trends In Immunology 2018, 39: 862-873. PMID: 30301592, PMCID: PMC6218297, DOI: 10.1016/j.it.2018.09.003.Peer-Reviewed Original ResearchConceptsVector immunityEvolutionary ecologyEvolutionary forcesEvolutionary ecologistsGenetic plasticityVector-borne pathogensArthropod populationsAbiotic factorsMolecular immunologistsMicrobial assaultImmune systemInnate defenseRecent scientific breakthroughsEcologyEcologistsImmune responsePathogenicityImmunityPathogensPlasticityDefenseToleranceResistanceScientific breakthroughsUBXN3B 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 recruitmentResponseSmall Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus
Beloor J, Maes N, Ullah I, Uchil P, Jackson A, Fikrig E, Lee SK, Kumar P. Small Interfering RNA-Mediated Control of Virus Replication in the CNS Is Therapeutic and Enables Natural Immunity to West Nile Virus. Cell Host & Microbe 2018, 23: 549-556.e3. PMID: 29606496, PMCID: PMC6074029, DOI: 10.1016/j.chom.2018.03.001.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionCell-mediated immune responsesLate-stage therapySubsequent WNV infectionWNV-infected miceLong-term immunityNile virusWNV E proteinViral burdenIntranasal routeVirus clearanceVirus infectionImmune responseMice succumbPeripheral tissuesNatural immunitySurvival rateDisease resultsDay 9Virus replicationInfectionImmunityCNSVirusDaily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells
Silver AC, Buckley SM, Hughes ME, Hastings AK, Nitabach MN, Fikrig E. Daily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells. Heliyon 2018, 4: e00579. PMID: 29862343, PMCID: PMC5968137, DOI: 10.1016/j.heliyon.2018.e00579.Peer-Reviewed Original ResearchAdherent splenocytesToll-like receptor expressionMRNA levelsProtein levelsSplenic immune cellsToll-like receptorsDependent immune responsesZeitgeber time (ZT) 1Adherent cell populationDendritic cellsTLR3 ligandTLR ligandsCytokine expressionSplenocyte populationImmune cellsReceptor expressionImmune responseSplenic macrophagesB cellsRhythmic expressionCell populationsTLRSplenocytesDaily light-dark cycleCircadian rhythm
2017
Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization
Narasimhan S, Schuijt TJ, Abraham NM, Rajeevan N, Coumou J, Graham M, Robson A, Wu MJ, Daffre S, Hovius JW, Fikrig E. Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization. Nature Communications 2017, 8: 184. PMID: 28775250, PMCID: PMC5543126, DOI: 10.1038/s41467-017-00208-0.Peer-Reviewed Original ResearchConceptsB. burgdorferi colonizationTick gutImmune responseRNA interference-mediated silencingGut microbiomeLyme disease agentBorrelia burgdorferiB. burgdorferiGutTick proteinsVivo resultsBurgdorferiPixRAbrogationTick Ixodes scapularisArthropod vectorsDisease agentsGut proteinsIxodes scapularisAlterationsGut genesMicrobiomeTick biologyMiceBacterial biofilm formationAn essential role of PI3K in the control of West Nile virus infection
Wang L, Yang L, Fikrig E, Wang P. An essential role of PI3K in the control of West Nile virus infection. Scientific Reports 2017, 7: 3724. PMID: 28623344, PMCID: PMC5473900, DOI: 10.1038/s41598-017-03912-5.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionPI3K inhibitorsPI3KVirus infectionImmune responseK inhibitorsType I IFN responseAntiviral immune responseI IFN responseCatalytic subunit p110δTNF-α protein productionPrimary mouse macrophagesFlaviviral infectionsAntiviral immunityIFN responseViral titersClass I PI3KAntiviral roleMRNA expressionPI3K activityIFNProtein expressionInfectionMouse macrophagesCell proliferation