2022
CD55 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 ResearchMeSH KeywordsAnimalsBlood Group AntigensBorreliaCytokinesHumansImmune EvasionMiceRelapsing FeverRodentiaConceptsRole 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 expression
2020
A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis
Gupta A, Arora G, Rosen CE, Kloos Z, Cao Y, Cerny J, Sajid A, Hoornstra D, Golovchenko M, Rudenko N, Munderloh U, Hovius JW, Booth CJ, Jacobs-Wagner C, Palm NW, Ring AM, Fikrig E. A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis. PLOS Pathogens 2020, 16: e1009030. PMID: 33175909, PMCID: PMC7657531, DOI: 10.1371/journal.ppat.1009030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiCytokinesGene LibraryHumansLyme DiseaseMiceMice, Inbred BALB CConceptsPeptidoglycan recognition protein 1B. burgdorferi infectionB. burgdorferiBurgdorferi infectionHost responseLow serum IgG levelsCommon vector-borne illnessDiverse host responsesSerum IgG levelsProtein 1Vector-borne illnessImmune dysregulationIgG levelsBorreliacidal activityBurgdorferi sensu latoHuman extracellular proteinsSpirochete burdenTick biteB. burgdorferi sensu latoSpirochete Borrelia burgdorferiNervous systemLyme borreliosisLyme diseaseInfectionBorrelia burgdorferi
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 adhesionLiverBerghei
2015
Nlrp6 regulates intestinal antiviral innate immunity
Wang P, Zhu S, Yang L, Cui S, Pan W, Jackson R, Zheng Y, Rongvaux A, Sun Q, Yang G, Gao S, Lin R, You F, Flavell R, Fikrig E. Nlrp6 regulates intestinal antiviral innate immunity. Science 2015, 350: 826-830. PMID: 26494172, PMCID: PMC4927078, DOI: 10.1126/science.aab3145.Peer-Reviewed Original ResearchConceptsI/III interferonIntestinal antiviral innate immunityEncephalomyocarditis virusEnteric virus infectionType I/III interferonsGut microbiota homeostasisAntiviral innate immunityViral RNA sensorsViral loadControl miceVirus infectionGastrointestinal tractMicrobiota homeostasisSimilar mortalityIII interferonsAntibacterial immunityInnate immunityIntestinal tractRNA helicase DHX15MiceViral RNANLRP6Murine norovirus-1RNA sensorsMortality
2014
Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus
Qian F, Thakar J, Yuan X, Nolan M, Murray KO, Lee WT, Wong SJ, Meng H, Fikrig E, Kleinstein SH, Montgomery RR. Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus. Viral Immunology 2014, 27: 39-47. PMID: 24605787, PMCID: PMC3949440, DOI: 10.1089/vim.2013.0074.Peer-Reviewed Original ResearchConceptsWest Nile virusSevere infectionsImmune markersIL-4IL-4 levelsSerum cytokine levelsSerum IL-4Nile virusSignificant risk factorsImmune system statusPeripheral blood cellsSevere neurological diseaseCytokine levelsAntibody levelsImmune statusRisk factorsHealthy subjectsStratified cohortWNV infectionNeurological diseasesInfectionAltered expression levelsBlood cellsAltered gene expression patternsHost susceptibility
2012
Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection
Sukumaran B, Ogura Y, Pedra JH, Kobayashi KS, Flavell RA, Fikrig E. Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection. Pathogens And Disease 2012, 66: 211-219. PMID: 22747758, PMCID: PMC3530031, DOI: 10.1111/j.1574-695x.2012.01001.x.Peer-Reviewed Original ResearchConceptsRip2-deficient miceHuman granulocytic anaplasmosisNOD-like receptorsPhagocytophilum infectionTick-borne infectious diseaseNOD1/NOD2Obligate intracellular bacterium Anaplasma phagocytophilumInflammatory protein-2Host immune responseInnate immune pathwaysProtein 2Anaplasma phagocytophilum infectionHuman primary neutrophilsBacterium Anaplasma phagocytophilumHigh bacterial loadWild-type controlsImmune controlIL-12Immune clearanceImmune responseImmune pathwaysHost responseKC responsesHost defenseInfectious diseasesThe Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity
Silver AC, Arjona A, Walker WE, Fikrig E. The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity. Immunity 2012, 36: 251-261. PMID: 22342842, PMCID: PMC3315694, DOI: 10.1016/j.immuni.2011.12.017.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Receptor 9Adaptive immune responsesInnate immune systemCircadian molecular clockSepsis inductionTLR9 expressionTLR9 ligandsImmune responseVaccination modelAdaptive immunityMouse modelImmune systemDisease severityHomeostatic processesCircadian rhythmBiologic processesDirect molecular linkMolecular linkRhythmSepsisImmunotherapyImmunoprophylaxisExpressionInnate
2010
Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults
Dunne DW, Shaw A, Bockenstedt LK, Allore HG, Chen S, Malawista SE, Leng L, Mizue Y, Piecychna M, Zhang L, Towle V, Bucala R, Montgomery RR, Fikrig E. Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults. PLOS ONE 2010, 5: e11343. PMID: 20596538, PMCID: PMC2893205, DOI: 10.1371/journal.pone.0011343.Peer-Reviewed Original ResearchConceptsNon-immunosuppressed adultsMIF levelsImmunosuppressive medicationsAutoimmune diseasesIL-8Cytokine productionMonocyte Toll-like receptor (TLR) expressionInnate immunityToll-like receptor expressionEnhanced innate immune responseAltered host immunityAutoimmune disease groupDownstream cytokine productionNon-immunosuppressed individualsUnderlying autoimmune diseaseFeatures of patientsHuman peripheral blood monocytesTLR4 surface expressionCytokine IL-8Number of patientsSurface expressionPeripheral blood monocytesInnate immune responseRisk of infectionImmunosuppressed adultsAge-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response
Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, Allore HG, Montgomery RR, Shaw AC. Age-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response. The Journal Of Immunology 2010, 184: 2518-2527. PMID: 20100933, PMCID: PMC3867271, DOI: 10.4049/jimmunol.0901022.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntibodies, ViralCytokinesDendritic CellsFemaleFlow CytometryHumansInfluenza A Virus, H1N1 SubtypeInfluenza VaccinesInterleukin-12 Subunit p40Interleukin-6Linear ModelsMaleMiddle AgedReverse Transcriptase Polymerase Chain ReactionToll-Like ReceptorsTumor Necrosis Factor-alphaYoung AdultConceptsPrimary human dendritic cellsDendritic cellsHuman dendritic cellsMyeloid DCsPlasmacytoid DCsCytokine productionTLR functionTNF-alphaIntracellular cytokine productionPoor Ab responsesInfluenza vaccine responsesMyeloid dendritic cellsPlasmacytoid dendritic cellsYoung individualsIntracellular cytokine stainingIL-12 productionIFN-alpha productionTLR ligand stimulationTLR gene expressionInnate immune responseAge-Associated DecreaseTLR8 engagementInfluenza immunizationAge-associated effectsCytokine staining
2009
IL-10 Signaling Blockade Controls Murine West Nile Virus Infection
Bai F, Town T, Qian F, Wang P, Kamanaka M, Connolly TM, Gate D, Montgomery RR, Flavell RA, Fikrig E. IL-10 Signaling Blockade Controls Murine West Nile Virus Infection. PLOS Pathogens 2009, 5: e1000610. PMID: 19816558, PMCID: PMC2749443, DOI: 10.1371/journal.ppat.1000610.Peer-Reviewed Original ResearchConceptsIL-10 signalingIL-10WNV infectionWest Nile virusIL-10-deficient miceWest Nile virus infectionImportant cellular sourceSignificant human morbidityRNA flavivirusWNV pathogenesisInterleukin-10Antiviral cytokinesEtiologic rolePharmacologic blockadeDeficient miceT cellsVirus infectionPharmacologic meansTherapeutic strategiesViral infectionCellular sourceInfectionHuman morbidityNile virusMiceHuman innate immunosenescence: causes and consequences for immunity in old age
Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC. Human innate immunosenescence: causes and consequences for immunity in old age. Trends In Immunology 2009, 30: 325-333. PMID: 19541535, PMCID: PMC4067971, DOI: 10.1016/j.it.2009.05.004.Peer-Reviewed Original ResearchConceptsInnate immune system initiatesNatural killer T cellsOlder ageAntiviral cytokine productionKiller T cellsInnate immune responseInnate immune systemDendritic cellsNatural killerCytokine productionHuman immunosenescenceT cellsImmune responseAdaptive immunityImmune systemInnate immunityImmunityAgeCellsDiverse cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfectionToll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing
Town T, Bai F, Wang T, Kaplan AT, Qian F, Montgomery RR, Anderson JF, Flavell RA, Fikrig E. Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing. Immunity 2009, 30: 242-253. PMID: 19200759, PMCID: PMC2707901, DOI: 10.1016/j.immuni.2008.11.012.Peer-Reviewed Original ResearchConceptsToll-like receptor 7West Nile virusReceptor 7WNV infectionImmune cell infiltrationLethal WNV infectionMyeloid differentiation factorIL-23 p19IL-23 responsesIL-12 p40West Nile encephalitisIL-12 p35Infected target cellsHost defense mechanismsRNA flavivirusInnate cytokinesWNV encephalitisInterleukin-12Cell infiltrationImmune cellsTarget organsVariable severityMiceTarget cellsTissue concentrations
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 responseDysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly
Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE, Fikrig E, Montgomery RR. Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly. Journal Of Virology 2008, 82: 7613-7623. PMID: 18508883, PMCID: PMC2493309, DOI: 10.1128/jvi.00618-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overCell Adhesion MoleculesCell LineCells, CulturedCytokinesFemaleHumansImmunity, InnateLectins, C-TypeMacrophagesMaleMiddle AgedNorth AmericaProtein BindingReceptors, Cell SurfaceSTAT1 Transcription FactorToll-Like Receptor 3Viral Envelope ProteinsWest Nile FeverWest Nile virusConceptsInnate immune responseToll-like receptor 3Intercellular adhesion molecule 3West Nile virusImmune responseYoung donorsC-type lectin dendritic cell-specific intercellular adhesion molecule 3Dendritic cell-specific intercellular adhesion molecule 3Nile virusBlood-brain barrierWNV envelope proteinSevere neurological diseaseResponsiveness of macrophagesPrimary human macrophagesCytokine levelsOlder donorsWNV infectionNeurological diseasesReceptor 3Human macrophagesOlder individualsElevated levelsMacrophagesMolecule 3Significant differencesSalp15 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 vectorICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System
Dai J, Wang P, Bai F, Town T, Fikrig E. ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System. Journal Of Virology 2008, 82: 4164-4168. PMID: 18256150, PMCID: PMC2292986, DOI: 10.1128/jvi.02621-07.Peer-Reviewed Original ResearchConceptsWest Nile virusICAM-1Control animalsWest Nile virus neuroinvasionBlood-brain barrier leakagePathogenesis of encephalitisNile virusBlood-brain barrierLow viral loadWest Nile encephalitisCentral nervous systemICAM-1 participatesVirus neuroinvasionNeuronal damageLeukocyte infiltrationViral encephalitisViral loadBarrier leakageViral infectionNervous systemEncephalitisMiceICAMVirusAnimals
2007
West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses
Arjona A, Ledizet M, Anthony K, Bonafé N, Modis Y, Town T, Fikrig E. West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses. The Journal Of Immunology 2007, 179: 8403-8409. PMID: 18056386, DOI: 10.4049/jimmunol.179.12.8403.Peer-Reviewed Original ResearchConceptsWest Nile virusInnate immune responseReceptor-interacting protein 1Immune responseMajor structural proteinVirus-associated molecular patternsDipteran cellsViral replication intermediatesRNA helicasesAdaptor molecule TRIFReplication intermediatesStructural proteinsWNV envelope proteinGlycosylation patternsMolecular patternsAntiviral stateGlycosylation profileProtein 1Murine macrophagesProinflammatory cytokinesCytokine productionImmunosuppressive effectsDsRNAImmune cellsEnvelope protein
2001
Coinfection with Borrelia burgdorferi and the Agent of Human Granulocytic Ehrlichiosis Alters Murine Immune Responses, Pathogen Burden, and Severity of Lyme Arthritis
Thomas V, Anguita J, Barthold S, Fikrig E. Coinfection with Borrelia burgdorferi and the Agent of Human Granulocytic Ehrlichiosis Alters Murine Immune Responses, Pathogen Burden, and Severity of Lyme Arthritis. Infection And Immunity 2001, 69: 3359-3371. PMID: 11292759, PMCID: PMC98295, DOI: 10.1128/iai.69.5.3359-3371.2001.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisLyme arthritisDual infectionBacterial burdenImmune responseTumor necrosis factor-alpha levelsB. burgdorferiElevated IL-6 levelsNecrosis factor-alpha levelsGranulocytic ehrlichiosisIL-6 levelsAgent of HGEMurine immune responseBorrelia burgdorferiTick-borne illnessMurine Lyme arthritisSevere Lyme arthritisCoinfection of miceIFN-gamma receptor expressionInfected miceInterleukin-12Receptor expressionGamma interferonArthritisPathogen burden
2000
Gamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia
Akkoyunlu M, Fikrig E. Gamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia. Infection And Immunity 2000, 68: 1827-1833. PMID: 10722570, PMCID: PMC97354, DOI: 10.1128/iai.68.4.1827-1833.2000.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteremiaConcanavalin ACytokinesDisease ProgressionDose-Response Relationship, DrugEhrlichiosisEnzyme-Linked Immunosorbent AssayFemaleHL-60 CellsHumansImmunoglobulin GInterferon-gammaMiceMice, Inbred C3HNeutrophilsReverse Transcriptase Polymerase Chain ReactionRickettsiaSpleenTime FactorsT-LymphocytesConceptsIFN-gamma-deficient miceHuman granulocytic ehrlichiosisIFN-gamma levelsDay 8Cytokine responsesIFN-gammaGamma interferonCells/HGE bacteriaGranulocytic ehrlichiosisIFN-gamma-independent mechanismMurine cytokine responsesTime pointsAgent of HGEMore IFN-gammaC3H/HeNLess interleukin-4IFN-gamma responsesMurine infection modelLater time pointsObligate intracellular bacteriumTh1 phenotypeC57BL/6 miceDNA burdenImmunocompetent mice