2024
Vaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches
Johnson E, Hart T, Fikrig E. Vaccination to Prevent Lyme Disease: A Movement Towards Anti-Tick Approaches. The Journal Of Infectious Diseases 2024, 230: s82-s86. PMID: 39140718, PMCID: PMC11322886, DOI: 10.1093/infdis/jiae202.Peer-Reviewed Original ResearchConceptsTransmission of tick-borne pathogensTick-borne pathogensIxodes spp ticksInhibited tick feedingTick feedingDisease vaccineTick vectorWildlife reservoirsOuter surface protein ALyme disease vaccineLyme diseaseTicksBorrelia burgdorferiLyme disease casesPreventing Lyme diseasePathogensFood and Drug AdministrationSurface protein AOspA-based vaccinesVaccineFeedingLymeProtein AFoodPrevent transmissionThe 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 ResearchConceptsSuppress 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 infectionmosGILT controls innate immunity and germ cell development in Anopheles gambiae
Arora G, Tang X, Cui Y, Yang J, Chuang Y, Joshi J, Sajid A, Dong Y, Cresswell P, Dimopoulos G, Fikrig E. mosGILT controls innate immunity and germ cell development in Anopheles gambiae. BMC Genomics 2024, 25: 42. PMID: 38191283, PMCID: PMC10775533, DOI: 10.1186/s12864-023-09887-0.Peer-Reviewed Original ResearchConceptsGerm cell developmentAnopheles gambiaeCell developmentOvarian developmentReductase-like proteinWild-type mosquitoesPlasmodium life cycleBiological controlGrowth genesEssential regulatorRNA sequencingA. gambiaeGenesGambiaeAltered expressionImpaired ovarian developmentMosquito vectorsLife cycleMosquitoesImmune activationPlasmodium infectionTranscriptomeOogenesisRegulatorProteinmRNA 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
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 hostsA ticking time bomb hidden in plain sight
Narasimhan S, Fish D, Pedra J, Pal U, Fikrig E. A ticking time bomb hidden in plain sight. Science Translational Medicine 2023, 15: eadi7829. PMID: 37851823, DOI: 10.1126/scitranslmed.adi7829.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsBulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite
Tang X, Lynn G, Cui Y, Cerny J, Arora G, Tomayko M, Craft J, Fikrig E. Bulk and single-nucleus RNA sequencing highlight immune pathways induced in individuals during an Ixodes scapularis tick bite. Infection And Immunity 2023, 91: e00282-23. PMID: 37846980, PMCID: PMC10652856, DOI: 10.1128/iai.00282-23.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceFeeding BehaviorGuinea PigsHumansIxodesRNA, Small NuclearTick BitesConceptsRNA sequencingSingle-nucleus RNA sequencingBulk RNA sequencingInterleukin-17 signalingPlatelet activation pathwaysLaboratory guinea pigsSnRNA-seqHippo signalingIndividual genesPeripheral bloodTick biteAdaptive immunityAnti-tick vaccinesGuidance pathwayImmune pathwaysNew biomarkersHost responseGuinea pigsHematophagous arthropodsHost defenseCell adhesionTick attachmentNovel insightsTick feedingPhysiological consequencesDevelopment 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 platformSpecific 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 ResearchCroquemort elicits activation of the immune deficiency pathway in ticks
O’Neal A, Singh N, Rolandelli A, Laukaitis H, Wang X, Shaw D, Young B, Narasimhan S, Dutta S, Snyder G, Samaddar S, Marnin L, Butler L, Mendes M, Paz F, Valencia L, Sundberg E, Fikrig E, Pal U, Weber D, Pedra J. Croquemort elicits activation of the immune deficiency pathway in ticks. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2208673120. PMID: 37155900, PMCID: PMC10193931, DOI: 10.1073/pnas.2208673120.Peer-Reviewed Original ResearchConceptsImmune deficiency (IMD) pathwayIMD pathwayNon-insect arthropodsPeptidoglycan recognition proteinsJun N-terminal kinaseN-terminal kinaseArthropod immunityMembrane localizationRecognition proteinsLyme disease spirocheteEcdysteroid synthesisMicrobial moietiesDistinct mechanismsProteinArthropodsPathwayHost defenseElicit activationCroquemortPancrustaceaHomologInsectsActivationCrustaceansKinaseMalaria: influence of Anopheles mosquito saliva on Plasmodium infection
Arora G, Chuang Y, Sinnis P, Dimopoulos G, Fikrig E. Malaria: influence of Anopheles mosquito saliva on Plasmodium infection. Trends In Immunology 2023, 44: 256-265. PMID: 36964020, PMCID: PMC10074230, DOI: 10.1016/j.it.2023.02.005.Peer-Reviewed Original ResearchConceptsAnopheles salivaPlasmodium infectionInfected female mosquitoesMosquito salivary proteinsLocal host responseComponents of salivaMosquito salivaTherapeutic strategiesHost responsePlasmodium sporozoitesVector salivaPlasmodium protozoaBlood vesselsSalivaFemale mosquitoesBlood mealAnopheline mosquitoesInfectionMalariaVector-borne diseasesSkinHost-pathogen interactionsSporozoitesSalivary proteinsMosquitoesDome1–JAK–STAT signaling between parasite and host integrates vector immunity and development
Rana V, Kitsou C, Dutta S, Ronzetti M, Zhang M, Bernard Q, Smith A, Tomás-Cortázar J, Yang X, Wu M, Kepple O, Li W, Dwyer J, Matias J, Baljinnyam B, Oliver J, Rajeevan N, Pedra J, Narasimhan S, Wang Y, Munderloh U, Fikrig E, Simeonov A, Anguita J, Pal U. Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development. Science 2023, 379: eabl3837. PMID: 36634189, PMCID: PMC10122270, DOI: 10.1126/science.abl3837.Peer-Reviewed Original ResearchConceptsBlood meal acquisitionMetazoan developmentTick receptorArthropod immunityMammalian hostsSignaling pathwaysReceptor motifEvolutionary dependenceVectorial competenceStem cellsCommunication pathwaysPathwayCritical roleVector immunityHostHigh affinityGenomeAntimicrobial componentsHedgehogJAKMotifMetamorphosisImmunityParasitesPhysiology
2022
A tick C1q protein alters infectivity of the Lyme disease agent by modulating interferon γ
Tang X, Arora G, Matias J, Hart T, Cui Y, Fikrig E. A tick C1q protein alters infectivity of the Lyme disease agent by modulating interferon γ. Cell Reports 2022, 41: 111673. PMID: 36417869, PMCID: PMC9909562, DOI: 10.1016/j.celrep.2022.111673.Peer-Reviewed Original ResearchTick transmission of Borrelia burgdorferi to the murine host is not influenced by environmentally acquired midgut microbiota
Narasimhan S, Rajeevan N, Graham M, Wu MJ, DePonte K, Marion S, Masson O, O’Neal A, Pedra JHF, Sonenshine DE, Fikrig E. Tick transmission of Borrelia burgdorferi to the murine host is not influenced by environmentally acquired midgut microbiota. Microbiome 2022, 10: 173. PMID: 36253842, PMCID: PMC9575305, DOI: 10.1186/s40168-022-01378-w.Peer-Reviewed Original ResearchCD55 Facilitates Immune Evasion by Borrelia crocidurae, an Agent of Relapsing Fever
Arora G, Lynn GE, Tang X, Rosen CE, Hoornstra D, Sajid A, Hovius JW, Palm NW, Ring AM, Fikrig E. CD55 Facilitates Immune Evasion by Borrelia crocidurae, an Agent of Relapsing Fever. MBio 2022, 13: e01161-22. PMID: 36036625, PMCID: PMC9600505, DOI: 10.1128/mbio.01161-22.Peer-Reviewed Original ResearchConceptsRole of CD55Fever infectionImmune evasionSurface of erythrocytesRosette formationB. crociduraeB. persicaHost factorsBorrelia crociduraeAcute febrile illnessInflammatory cytokine levelsElevated proinflammatory cytokinesExpression of CD55Causative agentErythrocyte rosette formationFacilitates Immune EvasionComplement-mediated lysisHost-pathogen interactionsCytokine levelsFebrile illnessSignificant morbidityProinflammatory cytokinesHigh-throughput screenC5a levelsCD55 expressionUse of host lipids by the Lyme disease spirochete may lead to biomarkers
Arora G, Hart T, Fikrig E. Use of host lipids by the Lyme disease spirochete may lead to biomarkers. Journal Of Clinical Investigation 2022, 132: e158254. PMID: 35289311, PMCID: PMC8920323, DOI: 10.1172/jci158254.Peer-Reviewed Original ResearchConceptsB. burgdorferi infectionLyme diseaseBurgdorferi infectionCareful clinical assessmentCommon tick-borne diseaseAnti-lipid antibodiesProduction of antibodiesTick-borne diseaseHost lipidsAntibody titersLyme disease agent Borrelia burgdorferiClinical assessmentCurrent biomarkersMurine modelDiseaseSerum samplesLyme disease spirocheteAntibodiesBorrelia burgdorferiInfectionBiomarkersPatientsLipidsSyphilisPhosphatidic acid
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 ResearchConceptsLocal 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 ResearchConceptsTick 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 ResearchConceptsTick-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 inductionThe Lyme Disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector
Tang X, Cao Y, Arora G, Hwang J, Sajid A, Brown CL, Mehta S, Marín-López A, Chuang YM, Wu MJ, Ma H, Pal U, Narasimhan S, Fikrig E. The Lyme Disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector. ELife 2021, 10: e72568. PMID: 34783654, PMCID: PMC8639152, DOI: 10.7554/elife.72568.Peer-Reviewed Original ResearchConceptsReceptor-mediated signalingAdiponectin receptorsAdiponectinLyme disease agentLyme disease spirochetePhospholipid metabolismPhosphatidylserine synthase ITick gutReceptor-like proteinMammalian homeostasisArthropod vectorsDisease agentsRNAi assaysRNA interferenceAlternative pathwaySynthase IPathwayMetabolic pathwaysTicksInfection