2020
CXCL10 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 populationsArthritisFootpad
2019
Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils
Hastings AK, Uraki R, Gaitsch H, Dhaliwal K, Stanley S, Sproch H, Williamson E, MacNeil T, Marin-Lopez A, Hwang J, Wang Y, Grover JR, Fikrig E. Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils. Journal Of Virology 2019, 93: 10.1128/jvi.00395-19. PMID: 30971475, PMCID: PMC6580965, DOI: 10.1128/jvi.00395-19.Peer-Reviewed Original ResearchConceptsVirus infectionBite siteMosquito salivaImmune cellsZika virusLocal immune environmentMosquito bite siteZika virus pathogenesisEarly viral replicationZika virus infectionFactor 1Pathogenesis of flavivirusesVirus-infected mosquitoesVirus-induced pathogenesisCXCL2 expressionImmune environmentPassive immunizationZIKV pathogenesisImmune microenvironmentAntibody responseZIKV replicationVirus pathogenesisMosquito bitesPrimary mouse neutrophilsImmune system
2012
IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis
Wang P, Bai F, Zenewicz LA, Dai J, Gate D, Cheng G, Yang L, Qian F, Yuan X, Montgomery RR, Flavell RA, Town T, Fikrig E. IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis. PLOS ONE 2012, 7: e44153. PMID: 22952908, PMCID: PMC3429482, DOI: 10.1371/journal.pone.0044153.Peer-Reviewed Original ResearchConceptsWild-type miceCentral nervous systemIL-22Viral loadNeutrophil migrationType miceWest Nile virus encephalitisSimilar viral loadsLethal WNV infectionIL-22 signalingHost immune responseWNV neuroinvasionVirus encephalitisCXCR2 ligandsLeukocyte infiltrateProinflammatory cytokinesChemokine receptorsImmune responseWNV infectionViral infectionNervous systemSignaling contributesExtracellular pathogensNon-redundant roleWT leukocytes
2011
A 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
A Paradoxical Role for Neutrophils in the Pathogenesis of West Nile Virus
Bai F, Kong KF, Dai J, Qian F, Zhang L, Brown CR, Fikrig E, Montgometry R. A Paradoxical Role for Neutrophils in the Pathogenesis of West Nile Virus. The Journal Of Infectious Diseases 2010, 202: 1804-1812. PMID: 21050124, PMCID: PMC3053000, DOI: 10.1086/657416.Peer-Reviewed Original ResearchConceptsWest Nile virusPolymorphonuclear leukocytesWNV infectionNile virusHigh viremiaViral clearanceEarly deathEarly infectionControl groupProtective roleBiphasic responseInnate immunityViral pathogenesisInfectionMiceViremiaPathogenesisParadoxical roleEfficient replicationVirusCXCL1CXCL2ChemokinesCXCR2NeutrophilsAnaplasma phagocytophilum AptA modulates Erk1/2 signalling
Sukumaran B, Mastronunzio JE, Narasimhan S, Fankhauser S, Uchil PD, Levy R, Graham M, Colpitts TM, Lesser CF, Fikrig E. Anaplasma phagocytophilum AptA modulates Erk1/2 signalling. Cellular Microbiology 2010, 13: 47-61. PMID: 20716207, PMCID: PMC3005019, DOI: 10.1111/j.1462-5822.2010.01516.x.Peer-Reviewed Original ResearchConceptsA. phagocytophilum infectionPhagocytophilum infectionCommon tick-borne diseasesHuman granulocytic anaplasmosisActivation of ERK1/2ERK1/2 mitogen-activated protein kinasesA. phagocytophilum survivalPolymorphonuclear leucocytesMitogen-activated protein kinaseHuman neutrophilsObligate intracellular pathogensGranulocytic anaplasmosisIntracellular pathogensTick-borne diseasesInfectionERK1/2 activationAnaplasma phagocytophilumVimentinSurvivalActivationBacterial inclusionsHost proteinsIntermediate filament protein vimentinVirulence proteinsProtein vimentin
2009
Human 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 cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfectionInhibition 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 ResearchConceptsPolymorphonuclear 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
Anaplasma phagocytophilum Increases Cathepsin L Activity, Thereby Globally Influencing Neutrophil Function
Thomas V, Samanta S, Fikrig E. Anaplasma phagocytophilum Increases Cathepsin L Activity, Thereby Globally Influencing Neutrophil Function. Infection And Immunity 2008, 76: 4905-4912. PMID: 18765732, PMCID: PMC2573316, DOI: 10.1128/iai.00851-08.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumCathepsin LCathepsinsCysteine EndopeptidasesEhrlichiosisElectrophoretic Mobility Shift AssayGene Expression Regulation, BacterialHL-60 CellsHomeodomain ProteinsHumansImmunoblottingImmunoprecipitationNeutrophilsNuclear ProteinsRepressor ProteinsReverse Transcriptase Polymerase Chain ReactionTranscription FactorsConceptsA. phagocytophilum infectionPhagocytophilum infectionCathepsin L activityNeutrophil functionA. phagocytophilumL activityHuman neutrophil peptides 1Polymorphonuclear leukocyte functionNeutrophil peptide-1Human granulocytic anaplasmosisTherapeutic optionsNeutrophil defenseLeukocyte functionCathepsin LPeptide-1InfectionObligate intracellular pathogensMarked reductionGranulocytic anaplasmosisIntracellular pathogensCDP activityHost oxidative burstAnaplasma phagocytophilumPhagocytophilumOxidative burst
2007
IL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model of human anaplasmosis
Pedra JH, Tao J, Sutterwala FS, Sukumaran B, Berliner N, Bockenstedt LK, Flavell RA, Yin Z, Fikrig E. IL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model of human anaplasmosis. Pathogens And Disease 2007, 50: 401-410. PMID: 17521390, DOI: 10.1111/j.1574-695x.2007.00270.x.Peer-Reviewed Original ResearchConceptsIL-12/23p40Deficient miceT cellsImmune responseHuman anaplasmosisTh1 immune responseIFN-gamma productionDay 6 postinfectionAnaplasma phagocytophilumA. phagocytophilum burdenIL-23Dendritic cellsIL-12Neutrophil numbersIFN-gammaMurine modelMicrobial agonistsPathogen clearanceDependent clearanceInfectious diseasesEarly susceptibilityPathogen eliminationCausative agentA. phagocytophilumIndependent mechanismsAnaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection
Thomas V, Fikrig E. Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection. Cellular Microbiology 2007, 9: 1730-1737. PMID: 17346310, DOI: 10.1111/j.1462-5822.2007.00908.x.Peer-Reviewed Original ResearchConceptsAnaplasma phagocytophilumPSGL-1Non-antibiotic strategiesHuman granulocytic anaplasmosisA. phagocytophilum infectionA. phagocytophilum-infected cellsTick-borne agentsPolymorphonuclear leucocytesPromyelocytic cell linePhagocytophilum infectionObligate intracellular pathogensInfectionTyrosine phosphorylationIntracellular pathogensGranulocytic anaplasmosisCell linesROCK1SykPhagocytophilumPhosphorylationNeutrophilsLeucocytesAntibodies
2006
Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum
Carlyon JA, Fikrig E. Mechanisms of evasion of neutrophil killing by Anaplasma phagocytophilum. Current Opinion In Hematology 2006, 13: 28-33. PMID: 16319684, DOI: 10.1097/01.moh.0000190109.00532.56.Peer-Reviewed Original ResearchConceptsApoptosis differentiation programMitochondrial membrane integrityA. phagocytophilumCaspase-3 activationBacterium altersMolecular machineryVacuolar membraneTranscription factorsDifferentiation programMammalian hostsSecretory vesiclesAnaplasma phagocytophilumCytoplasmic compartmentGene expressionPromoter activityAntiapoptotic genesNADPH oxidase assemblyOxidase assemblyNeutrophil gene expressionHost cellsBacterial uptakeNADPH oxidase componentsMechanisms of evasionMembrane integrityCytochrome b558
2005
Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection
Sukumaran B, Carlyon JA, Cai JL, Berliner N, Fikrig E. Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection. Infection And Immunity 2005, 73: 8089-8099. PMID: 16299303, PMCID: PMC1307096, DOI: 10.1128/iai.73.12.8089-8099.2005.Peer-Reviewed Original ResearchConceptsEarly transcriptional responseTranscriptional responseGene expressionHost cell gene expressionComprehensive DNA microarray analysisA. phagocytophilum infectionDNA microarray analysisObligate intracellular pathogensCell gene expressionCFLAR geneTNFSF10 geneA. phagocytophilum-infected neutrophilsCytoskeletal remodelingVesicular transportTranscriptional profilesHost pathwaysMicroarray analysisAntiapoptotic genesPromyelocytic cell lineDifferential expressionPhagocytophilum infectionHost cellsGenesHuman neutrophilsIntracellular pathogensEffects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels
Carlyon JA, Ryan D, Archer K, Fikrig E. Effects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels. Infection And Immunity 2005, 73: 7629-7636. PMID: 16239567, PMCID: PMC1273867, DOI: 10.1128/iai.73.11.7629-7636.2005.Peer-Reviewed Original ResearchConceptsFerritin protein levelsProtein levelsHL-60 cellsA. phagocytophilumAnaplasma phagocytophilumSerum-opsonized zymosanHuman granulocytic anaplasmosisA. phagocytophilum infectionInfected HL-60 cellsTime-dependent mannerObligate intracellular bacteriumFerritin levelsInfected miceA. phagocytophilum-infected miceMajor intracellular iron storage proteinFerritin heavy chainHuman promyelocytic HL-60 cellsNADPH oxidase assemblyNeutrophilsPromyelocytic HL-60 cellsMRNA expressionPhagocytophilum infectionIntracellular pathogensGranulocytic anaplasmosisIntracellular bacteriumModulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum
Pedra JH, Sukumaran B, Carlyon JA, Berliner N, Fikrig E. Modulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum. Genomics 2005, 86: 365-377. PMID: 16005178, DOI: 10.1016/j.ygeno.2005.05.008.Peer-Reviewed Original ResearchConceptsCell machineryA. phagocytophilum infectionTwo-dimensional differential gel electrophoresisSignal transduction genesNB4 promyelocytic leukemic cellsHigh-density oligoarraysDifferential gel electrophoresisPhagocytophilum infectionIron metabolism genesNF-kappaB genesTransduction genesObligate intracellular bacteriumApoptotic programTranscription factorsNegative obligate intracellular bacteriumCell adhesion moleculeAnaplasma phagocytophilumAntiapoptotic genesGenesIntracellular bacteriumNB4 cellsAffymetrix dataGel electrophoresisTranscriptionPromyelocytic leukemic cells
2004
CXCR2 Blockade Influences Anaplasma phagocytophilum Propagation but Not Histopathology in the Mouse Model of Human Granulocytic Anaplasmosis
Scorpio DG, Akkoyunlu M, Fikrig E, Dumler JS. CXCR2 Blockade Influences Anaplasma phagocytophilum Propagation but Not Histopathology in the Mouse Model of Human Granulocytic Anaplasmosis. MSphere 2004, 11: 963-968. PMID: 15358660, PMCID: PMC515272, DOI: 10.1128/cdli.11.5.963-968.2004.Peer-Reviewed Original ResearchConceptsHuman granulocytic anaplasmosisControl miceGranulocytic anaplasmosisC3H-scid miceInfected cellsTissue loadsObligate intracellular bacteriumNeutrophil recruitmentNeutrophil secretionAntibody blockadeChemokine inductionHepatic pathologyLiver histopathologyInterleukin-8Tissue injuryMouse modelControl animalsDay 14Intracellular bacteriumMiceInfectionAnaplasma phagocytophilumA. phagocytophilumHistopathologyNeutrophilsAnaplasma phagocytophilum Utilizes Multiple Host Evasion Mechanisms To Thwart NADPH Oxidase-Mediated Killing during Neutrophil Infection
Carlyon JA, Latif D, Pypaert M, Lacy P, Fikrig E. Anaplasma phagocytophilum Utilizes Multiple Host Evasion Mechanisms To Thwart NADPH Oxidase-Mediated Killing during Neutrophil Infection. Infection And Immunity 2004, 72: 4772-4783. PMID: 15271939, PMCID: PMC470610, DOI: 10.1128/iai.72.8.4772-4783.2004.Peer-Reviewed Original ResearchConceptsPhorbol myristate acetateUnique tropismA. phagocytophilumNADPH oxidase assemblyOxidative killingNADPH oxidaseAnaplasma phagocytophilumSerum-opsonized zymosanA. phagocytophilum infectionHost evasion mechanismNeutrophil infectionOxygen species productionEvasion mechanismsEtiologic agentNADPH oxidase complexHuman anaplasmosisNeutrophilsPhagocytophilum infectionSecondary activationMyristate acetateDependent decreaseInitial stimulationNeutrophil plasma membranesSpecies productionPhagocytophilum
2003
Invasion and survival strategies of Anaplasma phagocytophilum
Carlyon JA, Fikrig E. Invasion and survival strategies of Anaplasma phagocytophilum. Cellular Microbiology 2003, 5: 743-754. PMID: 14531890, DOI: 10.1046/j.1462-5822.2003.00323.x.Peer-Reviewed Original ResearchConceptsAnaplasma phagocytophilumA. phagocytophilumHuman granulocytic ehrlichiosisHostile intracellular environmentTick-borne zoonosisObligate intracellular bacteriumHost neutrophilsNeutrophil adhesionInnate immunityPolymorphonuclear leucocytesAetiological agentGranulocytic ehrlichiosisIntracellular bacteriumNeutrophilsMicrobicidal activityPhagocytophilumHost cellsProteolytic compoundsAcidic lysosomesBacteria-containing phagosomesKey playersLeucocytesImmunityEhrlichiosisPhagocytesMurine neutrophils require α1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum
Carlyon JA, Akkoyunlu M, Xia L, Yago T, Wang T, Cummings RD, McEver RP, Fikrig E. Murine neutrophils require α1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum. Blood 2003, 102: 3387-3395. PMID: 12869507, DOI: 10.1182/blood-2003-02-0621.Peer-Reviewed Original ResearchConceptsWild-type miceP-selectin glycoprotein ligand-1Murine neutrophilsCommon tick-borne diseaseAnaplasma phagocytophilumFuc-TIVHuman granulocytic ehrlichiosisPSGL-1 expressionTick-borne diseaseNeutrophil expressionInfection burdenMurine infectionNeutrophilsGranulocytic ehrlichiosisPhagocytophilum infectionMiceHuman neutrophilsSimilar molecular featuresInfectionProductive infectionSialidase treatmentLigand 1PhagocytophilumMolecular featuresFuc-TVII
2002
Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation
Carlyon JA, Chan WT, Galán J, Roos D, Fikrig E. Repression of rac2 mRNA Expression by Anaplasma phagocytophila Is Essential to the Inhibition of Superoxide Production and Bacterial Proliferation. The Journal Of Immunology 2002, 169: 7009-7018. PMID: 12471136, DOI: 10.4049/jimmunol.169.12.7009.Peer-Reviewed Original ResearchConceptsInfected HL-60 cellsHL-60 cellsAnaplasma phagocytophilaMRNA expressionNADPH oxidaseRetinoic acid-differentiated HL-60 cellsBacterial intracellular survivalHuman granulocytic ehrlichiosisNADPH oxidase activityNADPH oxidase activationQuantitative RT-PCRCMV immediate-early promoterInfected neutrophilsEtiologic agentGranulocytic ehrlichiosisRT-PCR analysisA. phagocytophilaIntracellular survivalSuperoxide productionOxidase activationNeutrophilsProtein expressionRT-PCRImmediate early promoterH postinfection