2024
The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872. PMID: 39121194, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchMeSH KeywordsAedesAnimalsCD47 AntigenFemaleHumansInsect ProteinsMosquito VectorsSalivary Proteins and PeptidesSkinZika VirusZika Virus InfectionConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
2021
Immunomodulation by Mosquito Salivary Protein AgSAP Contributes to Early Host Infection by Plasmodium
Arora G, Sajid A, Chuang YM, Dong Y, Gupta A, Gambardella K, DePonte K, Almeras L, Dimopolous G, Fikrig E. Immunomodulation by Mosquito Salivary Protein AgSAP Contributes to Early Host Infection by Plasmodium. MBio 2021, 12: e03091-21. PMID: 34903042, PMCID: PMC8669493, DOI: 10.1128/mbio.03091-21.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnophelesFemaleHumansInsect ProteinsMalariaMiceMice, Inbred C57BLMosquito VectorsPlasmodium bergheiPlasmodium falciparumSalivary Proteins and PeptidesSporozoitesConceptsLocal inflammatory responsePlasmodium berghei sporozoitesSalivary antigensInflammatory responseBerghei sporozoitesPlasmodium falciparumMosquito salivary proteinsPrevention of malariaLocal host responseAnopheline mosquitoesVertebrate hostsHost responseSaliva secretionVaccine developmentMalariaEpidemiological analysisGenerate antibodiesAntigenArthropod salivaDisease prevalenceInfectionSaliva componentsSporozoitesVector-borne diseasesDiseaseTick 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 strategiesProbing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine
Trentelman JJA, Tomás-Cortázar J, Knorr S, Barriales D, Hajdusek O, Sima R, Ersoz JI, Narasimhan S, Fikrig E, Nijhof AM, Anguita J, Hovius JW. Probing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine. Scientific Reports 2021, 11: 15745. PMID: 34344917, PMCID: PMC8333314, DOI: 10.1038/s41598-021-92538-9.Peer-Reviewed Original ResearchConceptsTick salivary gland proteinsLyme borreliosisVaccination studiesTick biteTick-borne encephalitis virusB. burgdorferi transmissionMultiple tick bitesYeast surface display libraryHuman infectious diseasesImmunization of rabbitsVaccination platformAnti-tick effectsAnti-tick vaccinesEncephalitis virusImmunodominant antigensInfectious diseasesNon-natural hostsTick immunityTick feedingImmunityBorreliosisBiteVaccineAntigenHuman serum
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 ResearchMeSH KeywordsAnimalsAnophelesInsect ProteinsMalariaMicePlasmodiumProtozoan ProteinsSalivary Proteins and PeptidesSporozoitesConceptsPassive immunizationCell traversal activityMosquito saliva proteinsMosquito salivary proteinsMosquito salivaNeutrophil chemotaxisProtein monoclonal antibodyProtective effectSporozoite glidingSporozoite infectivitySporozoite traversalMonoclonal antibodiesHost skinAnopheles mosquitoesProtein 1ImmunizationBlood mealSporozoitesSalivaMiceHost cellsSaliva proteinsSalivary proteinsAntiserumVertebrate hosts
2019
Aedes 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 proteinsVirusAntibodiesMosquitoesAntiserum
2018
Host-specific expression of Ixodes scapularis salivary genes
Narasimhan S, Booth CJ, DePonte K, Wu MJ, Liang X, Mohanty S, Kantor F, Fikrig E. Host-specific expression of Ixodes scapularis salivary genes. Ticks And Tick-borne Diseases 2018, 10: 386-397. PMID: 30545615, DOI: 10.1016/j.ttbdis.2018.12.001.Peer-Reviewed Original ResearchConceptsVector-host interactionsTick infestationI. scapularisReservoir hostsNon-reservoir hostsHost-specific expressionRodent reservoir hostsInfected ticksPathogen transmissionZoonotic cycleSalivary genesIxodes scapularisTicksNatural hostScapularisInfestationTick biteLyme diseaseBorrelia burgdorferiLarval stagesPathogensHostPeromyscus leucopusStrong immune responseSalivary transcriptomeImmunization 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 ResearchMeSH KeywordsAnimalsAnophelesDisease Models, AnimalImmunization, PassiveInsect ProteinsLiverMalariaMiceParasite LoadParasitemiaPlasmodium bergheiPlasmodium falciparumSalivary Proteins and PeptidesTreatment OutcomeConceptsPlasmodium infectionBerghei infectionMosquito salivary gland antigensPlasmodium berghei infectionPlasmodium circumsporozoite proteinSalivary gland antigensAnopheles salivaHumanized miceActive immunizationLiver burdenVaccine candidatesInfected mosquitoesCircumsporozoite proteinHost responseMurine dermisInfectionPlasmodium falciparumMiceSalivary glandsSaliva componentsImmunizationAnopheline mosquitoesMalariaAntiserumAntibodies
2016
Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection
Conway MJ, Londono-Renteria B, Troupin A, Watson AM, Klimstra WB, Fikrig E, Colpitts TM. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection. PLOS Neglected Tropical Diseases 2016, 10: e0004941. PMID: 27632170, PMCID: PMC5025043, DOI: 10.1371/journal.pntd.0004941.Peer-Reviewed Original ResearchMeSH KeywordsAedesAnimalsDengueDengue VirusFemaleHumansInsect ProteinsMiceSalivaSalivary GlandsSalivary Proteins and PeptidesU937 CellsConceptsSalivary gland extractsDengue virus infectionD7 proteinDengue virus type 1Virus type 1DENV envelope proteinAegypti salivaLymph nodesDENV infectionDENV virionsVirus infectionRelevant arbovirusesType 1InfectionHost skinBlood feedingEnvelope proteinNovel roleBinding assaysSalivaAedes aegyptiGland extractsPrimary vectorHPLC fractionsFeeding
2013
Factor Xa Activation of Factor V Is of Paramount Importance in Initiating the Coagulation System
Schuijt TJ, Bakhtiari K, Daffre S, DePonte K, Wielders SJ, Marquart JA, Hovius JW, van der Poll T, Fikrig E, Bunce MW, Camire RM, Nicolaes GA, Meijers JC, van ‘t Veer C. Factor Xa Activation of Factor V Is of Paramount Importance in Initiating the Coagulation System. Circulation 2013, 128: 254-266. PMID: 23817575, PMCID: PMC3826089, DOI: 10.1161/circulationaha.113.003191.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnticoagulantsArthropod ProteinsBlood CoagulationBlood Coagulation TestsDose-Response Relationship, DrugFactor VFactor XaFactor Xa InhibitorsFeeding BehaviorFibrinogenHumansIxodesMutagenesisProtein Structure, TertiaryRabbitsRecombinant ProteinsSalivary Proteins and PeptidesSurface Plasmon ResonanceThrombinAnopheles gambiae Circumsporozoite Protein–Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands
Wang J, Zhang Y, Zhao YO, Li MW, Zhang L, Dragovic S, Abraham NM, Fikrig E. Anopheles gambiae Circumsporozoite Protein–Binding Protein Facilitates Plasmodium Infection of Mosquito Salivary Glands. The Journal Of Infectious Diseases 2013, 208: 1161-1169. PMID: 23801601, PMCID: PMC3762383, DOI: 10.1093/infdis/jit284.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnophelesFemaleHost-Parasite InteractionsHumansMicePlasmodium bergheiProtein BindingProtozoan ProteinsSalivary GlandsSalivary Proteins and PeptidesConceptsMosquito salivary glandsCircumsporozoite proteinSalivary glandsPlasmodium organismsPlasmodium circumsporozoite proteinMosquito-borne diseasePlasmodium life cycleSubstantial morbidityPlasmodium infectionMosquito bitesFed bloodGut wallPlasmodium sporozoitesSalivary gland proteinsPlasmodium speciesParasite loadGlandBlood mealInfectionGland proteinsVertebrate hostsVivo bioassaySporozoitesInvasionProtein
2012
Immunization with adenoviral-vectored tick salivary gland proteins (SALPs) in a murine model of Lyme borreliosis
Ullmann AJ, Dolan MC, Sackal CA, Fikrig E, Piesman J, Zeidner NS. Immunization with adenoviral-vectored tick salivary gland proteins (SALPs) in a murine model of Lyme borreliosis. Ticks And Tick-borne Diseases 2012, 4: 160-163. PMID: 23141105, PMCID: PMC4306421, DOI: 10.1016/j.ttbdis.2012.08.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsArthropod ProteinsHeartIxodesLyme DiseaseMiceSalivary Proteins and PeptidesTick InfestationsUrinary BladderVaccinesConceptsTick salivary proteinsBorrelia burgdorferi infectionSalivary proteinsTick salivary gland proteinsSalivary gland proteinsTh1 responseImmunized miceSpecific immunityBurgdorferi infectionMurine modelSpirochete loadLyme borreliosisPrior exposureAdenovirus expression systemAdenoviral vectorTick challengeVaccinationMammalian hostsIxodes scapularisVertebrate hosts
2011
Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands
Liu L, Narasimhan S, Dai J, Zhang L, Cheng G, Fikrig E. Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands. EMBO Reports 2011, 12: 1196-1203. PMID: 21921936, PMCID: PMC3207102, DOI: 10.1038/embor.2011.177.Peer-Reviewed Original ResearchA Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent
Schuijt TJ, Coumou J, Narasimhan S, Dai J, DePonte K, Wouters D, Brouwer M, Oei A, Roelofs JJ, van Dam AP, van der Poll T, Veer C, Hovius JW, Fikrig E. A Tick Mannose-Binding Lectin Inhibitor Interferes with the Vertebrate Complement Cascade to Enhance Transmission of the Lyme Disease Agent. Cell Host & Microbe 2011, 10: 136-146. PMID: 21843870, PMCID: PMC3170916, DOI: 10.1016/j.chom.2011.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBorrelia burgdorferiCell Migration AssaysCloning, MolecularComplement Membrane Attack ComplexComplement Pathway, Mannose-Binding LectinFemaleGene SilencingHemolysisHumansImmunization, PassiveImmunotherapy, ActiveInsect ProteinsIxodesLarvaLyme DiseaseMiceMice, Inbred C3HMolecular Sequence DataNeutrophilsNymphPhagocytosisRabbitsRecombinant ProteinsSalivaSalivary Proteins and PeptidesSequence AlignmentConceptsComplement cascadeLyme disease agent Borrelia burgdorferiImpaired neutrophil phagocytosisTick salivary proteinsVector-borne pathogensLyme disease agentMammalian infectionVector colonizationVertebrate hostsTick midgutAlternative complement pathwayBorrelia transmissionComplement-mediated killingVector proteinNeutrophil phagocytosisEssential rolePathway inhibitorComplement pathwayDisease agentsSalivary proteinsBorrelia burgdorferiLectin inhibitorsProteinCascadeIxodes ticks
2010
Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks
Sultana H, Neelakanta G, Kantor FS, Malawista SE, Fish D, Montgomery RR, Fikrig E. Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks. Journal Of Experimental Medicine 2010, 207: 1727-1743. PMID: 20660616, PMCID: PMC2916137, DOI: 10.1084/jem.20100276.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnaplasma phagocytophilumAnimalsCell LineCell NucleusEnzyme InhibitorsGastrointestinal TractGene ExpressionGene Expression RegulationGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsInsect ProteinsIxodesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationPromoter Regions, GeneticProtein BindingRNA InterferenceRNA Polymerase IISalivary GlandsSalivary Proteins and PeptidesSignal TransductionTATA-Box Binding ProteinTranscription, GeneticConceptsRNA polymerase IIActin phosphorylationTATA box-binding proteinNuclear G-actinPhosphorylation of actinP21-activated kinaseA. phagocytophilumA. phagocytophilum survivalTick cell linesIxodes scapularis ticksPolymerase IIPhosphorylated actinGene crucialGbetagamma subunitsGene transcriptionFilamentous actinAnaplasma phagocytophilumGene expressionBacterial acquisitionScapularis ticksPhosphorylationG-actinIntracellular pathogensMedical importanceActin
2009
Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent
Dai J, Wang P, Adusumilli S, Booth CJ, Narasimhan S, Anguita J, Fikrig E. Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent. Cell Host & Microbe 2009, 6: 482-492. PMID: 19917502, PMCID: PMC2843562, DOI: 10.1016/j.chom.2009.10.006.Peer-Reviewed Original ResearchConceptsArthropod-borne pathogensTick-borne BorreliaTick salivary proteinsTick proteinsB. burgdorferiLyme diseaseDisease agentsTick-borne illnessB. burgdorferi infectionLyme disease agentHuman vaccinesSalp15Infection of miceB. burgdorferi antigensMicrobial toxinsMammalian hostsBorrelia burgdorferiPathogensMechanism of actionBurgdorferi infectionProtect miceMedical importanceBurgdorferiProtective capacityMiceInhibition of Neutrophil Function by Two Tick Salivary Proteins
Guo X, Booth CJ, Paley MA, Wang X, DePonte K, Fikrig E, Narasimhan S, Montgomery RR. Inhibition of Neutrophil Function by Two Tick Salivary Proteins. Infection And Immunity 2009, 77: 2320-2329. PMID: 19332533, PMCID: PMC2687334, DOI: 10.1128/iai.01507-08.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiFemaleGene Knockdown TechniquesHumansIntegrinsIxodesJointsMiceNeutrophilsSalivary Proteins and PeptidesSkinSuperoxidesConceptsPolymorphonuclear leukocytesPMN functionNumber of PMNPMN integrinsPMN adherenceNeutrophil functionSpirochete burdenTick salivary proteinsTick salivaLyme diseaseTick attachmentSalivary glandsBorrelia burgdorferiTick feedingCausative agentReduced levelsInhibitory proteinSalivaBlood mealAntihemostatic activityInfectionInhibitionSalivary proteinsHematophagous arthropodsTick Ixodes scapularis
2008
Preferential Protection of Borrelia burgdorferi Sensu Stricto by a Salp 15 Homologue in Ixodes ricinus Saliva
Hovius JW, Schuijt TJ, de Groot KA, Roelofs JJ, Oei GA, Marquart JA, de Beer R, Veer C, van der Poll T, Ramamoorthi N, Fikrig E, van Dam AP. Preferential Protection of Borrelia burgdorferi Sensu Stricto by a Salp 15 Homologue in Ixodes ricinus Saliva. The Journal Of Infectious Diseases 2008, 198: 1189-1197. PMID: 18752445, PMCID: PMC4317250, DOI: 10.1086/591917.Peer-Reviewed Original ResearchConceptsAntibody-mediated killingB. burgdorferiB. afzeliiB. gariniiEnzyme-linked immunosorbent assaySole causative agentBorrelia burgdorferi sensu latoBorrelia speciesSevere carditisOuter surface protein CImmune miceControl miceBorrelia burgdorferi sensu strictoBurgdorferi sensu latoSurface protein CSurvival advantageBurgdorferi sensu strictoSolid-phase overlayLyme borreliosisImmunosorbent assayProtein CCausative agentIxodes ticksBurgdorferiMiceThe Tick Salivary Protein Salp15 Inhibits the Killing of Serum-Sensitive Borrelia burgdorferi Sensu Lato Isolates
Schuijt TJ, Hovius JW, van Burgel ND, Ramamoorthi N, Fikrig E, van Dam AP. The Tick Salivary Protein Salp15 Inhibits the Killing of Serum-Sensitive Borrelia burgdorferi Sensu Lato Isolates. Infection And Immunity 2008, 76: 2888-2894. PMID: 18426890, PMCID: PMC2446733, DOI: 10.1128/iai.00232-08.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood Bactericidal ActivityBorrelia burgdorferi GroupCell MembraneComplement ActivationComplement Membrane Attack ComplexHumansIxodesSalivary Proteins and PeptidesConceptsComplement-mediated killingBurgdorferi-specific antibodiesBorrelia burgdorferiStrong protective effectSerum-sensitive isolatesNormal human serumBorrelia burgdorferi sensu latoBurgdorferi sensu latoProtective effectMembrane attack complexTick salivaLyme diseaseBorrelia burgdorferi sensu lato isolatesComplement complexI. scapularis Salp15B. burgdorferiSalp15Attack complexBurgdorferiHuman serumKillingSpirochetesIxodes scapularisIsolatesTicksSalp15 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