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 diseasesDisease
2020
An 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 interferenceIllnessTicksVaccination 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
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 proteinsVirusAntibodiesMosquitoesAntiserum28 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
Rev-erb Agonist Inhibits Chikungunya and O’nyong’nyong Virus Replication
Hwang J, Jiang A, Fikrig E. Rev-erb Agonist Inhibits Chikungunya and O’nyong’nyong Virus Replication. Open Forum Infectious Diseases 2018, 5: ofy315. PMID: 30568983, PMCID: PMC6293476, DOI: 10.1093/ofid/ofy315.Peer-Reviewed Original ResearchChikungunya virusSubset of patientsRecent global epidemicJoint painStructural protein synthesisSevere inflammationInflammatory responseMultiple alphavirusesViral RNA accumulationGlobal epidemicSynthetic agonistsVirus replicationCultured murine macrophagesMurine macrophagesSR9009AlphavirusesRelated virusesVirusProtein synthesisPainInflammationPatientsAgonistsMacrophagesRNA accumulationNeutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection
Baeza Garcia A, Siu E, Sun T, Exler V, Brito L, Hekele A, Otten G, Augustijn K, Janse CJ, Ulmer JB, Bernhagen J, Fikrig E, Geall A, Bucala R. Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection. Nature Communications 2018, 9: 2714. PMID: 30006528, PMCID: PMC6045615, DOI: 10.1038/s41467-018-05041-7.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAdoptive TransferAnimalsAntibodies, ProtozoanCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleGene ExpressionGerminal CenterImmunologic MemoryInterferon-gammaInterleukin-12Macrophage Migration-Inhibitory FactorsMalariaMalaria VaccinesMiceMice, Inbred BALB CPlasmodium bergheiProtein IsoformsProtozoan ProteinsRNA, ProtozoanTumor Necrosis Factor-alphaVaccines, DNAConceptsCD4 T cellsT cellsBlood-stage Plasmodium infectionMemory CD4 T cellsCytokine macrophage migration inhibitory factorMacrophage migration inhibitory factorBlood-stage patencyCD8 T cellsBlood-stage infectionMigration inhibitory factorHost inflammatory responseInflammatory markers TNFGerminal center responseMIF inhibitionTfh cellsAdoptive transferIL-12Protective immunityAntibody titersMalaria infectionPlasmodium infectionInflammatory responseSporozoite infectionCenter responseHost response
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 mechanismCircadian rhythms influence disease severity in a mouse model of sepsis (110.9)
Walker W, Bozzi A, Fikrig E. Circadian rhythms influence disease severity in a mouse model of sepsis (110.9). The Journal Of Immunology 2011, 186: 110.9-110.9. DOI: 10.4049/jimmunol.186.supp.110.9.Peer-Reviewed Original ResearchInflammatory responseMouse modelCircadian rhythmSerum proinflammatory cytokinesPuncture (CLP) mouse modelRisk of mortalitySeptic patientsSepsis inductionCecal ligationSepsis phenotypesEarly mortalityProinflammatory cytokinesSevere hypothermiaDisease scoreCLP modelDisease severitySepsisCreatine kinaseMortalityPatientsMiceRhythmSeverityTime 19Mammalian physiology
2009
Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody
Sultana H, Foellmer HG, Neelakanta G, Oliphant T, Engle M, Ledizet M, Krishnan MN, Bonafé N, Anthony KG, Marasco WA, Kaplan P, Montgomery RR, Diamond MS, Koski RA, Fikrig E. Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody. The Journal Of Immunology 2009, 183: 650-660. PMID: 19535627, PMCID: PMC3690769, DOI: 10.4049/jimmunol.0900093.Peer-Reviewed Original ResearchConceptsWest Nile virus envelope proteinWest Nile virusVirus envelope proteinDengue virusCross-reactive human monoclonal antibodiesBlood-brain barrier permeabilityEnvelope proteinWest Nile virus infectionNeutralization escape variantsNile virusWest Nile encephalitisNeutralization escape mutantsHuman monoclonal antibodyFatal neurological diseaseParental West Nile virusFusion loopEscape variantsInflammatory responseBarrier permeabilityLethal encephalitisMAb11Virus infectionHuman mAbsEscape mutantsNeurological diseases
2008
Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety
Yang X, Izadi H, Coleman AS, Wang P, Ma Y, Fikrig E, Anguita J, Pal U. Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety. Microbes And Infection 2008, 10: 1300-1308. PMID: 18725314, PMCID: PMC2648844, DOI: 10.1016/j.micinf.2008.07.029.Peer-Reviewed Original ResearchConceptsB mutantsWild-type B. burgdorferiP38 MAP kinase pathwayMAP kinase pathwayHuman synovial cellsSynovial cellsProtein moietyP38 MAP kinaseNF-kappaBLyme arthritisB operonKinase pathwayMAP kinaseRecombinant BmpAPro-inflammatory cytokines TNF-alphaCultured human synovial cellsLipopolysaccharide inhibitorMutantsCytokines TNF-alphaHost inflammatory responsePro-inflammatory responseCytokine responsesIL-1betaTNF-alphaInflammatory response
2007
Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion
Arjona A, Foellmer HG, Town T, Leng L, McDonald C, Wang T, Wong SJ, Montgomery RR, Fikrig E, Bucala R. Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion. Journal Of Clinical Investigation 2007, 117: 3059-3066. PMID: 17909632, PMCID: PMC1994625, DOI: 10.1172/jci32218.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMigration inhibitory factorViral neuroinvasionWest Nile virusInvolvement of MIFInhibitory factorProinflammatory cytokine macrophage migration inhibitory factorCytokine macrophage migration inhibitory factorWNV-infected miceBlood-brain barrierLife-threatening encephalitisWild-type miceAcute WNV infectionFlavivirus West Nile virusMIF expressionMIF levelsViral loadWNV encephalitisMIF actionPharmacotherapeutic approachesInflammatory responseWNV infectionCerebrospinal fluidSusceptible individualsInnate immunity
2004
Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis
Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nature Medicine 2004, 10: 1366-1373. PMID: 15558055, DOI: 10.1038/nm1140.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlood-Brain BarrierBrainEncephalitisImmunohistochemistryInflammationMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, FluorescencePermeabilityReceptors, Cell SurfaceSignal TransductionToll-Like Receptor 3Toll-Like ReceptorsTumor Necrosis Factor-alphaViral LoadWest Nile virusConceptsToll-like receptor 3West Nile virusWNV infectionViral loadInflammatory responseReceptor 3Blood-brain barrier compromiseTLR3-deficient miceWest Nile virus entryLethal WNV infectionBlood-brain barrierWild-type miceNeuronal injuryIntracerebroventricular administrationBrain infectionCytokine productionBrain penetrationTumor necrosisTLR3 stimulationLethal encephalitisBarrier compromiseVariable severityInfectionVirus entryNile virus