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-TVIIStructurally Distinct Requirements for Binding of P-selectin Glycoprotein Ligand-1 and Sialyl Lewis x to Anaplasma phagocytophilum and P-selectin*
Yago T, Leppänen A, Carlyon JA, Akkoyunlu M, Karmakar S, Fikrig E, Cummings RD, McEver RP. Structurally Distinct Requirements for Binding of P-selectin Glycoprotein Ligand-1 and Sialyl Lewis x to Anaplasma phagocytophilum and P-selectin*. Journal Of Biological Chemistry 2003, 278: 37987-37997. PMID: 12847092, DOI: 10.1074/jbc.m305778200.Peer-Reviewed Original Research
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 postinfectionDifferential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis
IJdo JW, Wu C, Telford SR, Fikrig E. Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis. Infection And Immunity 2002, 70: 5295-5298. PMID: 12183586, PMCID: PMC128253, DOI: 10.1128/iai.70.9.5295-5298.2002.Peer-Reviewed Original ResearchConceptsP44 geneDifferential expressionHuman granulocytic ehrlichiosisGene familyAntigenic variationHGE bacteriaTransmission feedingGranulocytic ehrlichiosisGenesHypervariable regionInfected C3H miceP44 expressionTick transmissionExpressionSCID miceC3H miceHGE infectionMurine modelInfected ticksSalivary glandsNymphal ticksMiceTicksEhrlichiosisBacteriaComparative reactivity of human sera to recombinant VlsE and other Borrelia burgdorferi antigens in class-specific enzyme-linked immunosorbent assays for Lyme borreliosis
Magnarelli LA, Lawrenz M, Norris SJ, Fikrig E. Comparative reactivity of human sera to recombinant VlsE and other Borrelia burgdorferi antigens in class-specific enzyme-linked immunosorbent assays for Lyme borreliosis. Journal Of Medical Microbiology 2002, 51: 649-655. PMID: 12171295, DOI: 10.1099/0022-1317-51-8-649.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assayIgG antibodiesErythema migransIgM antibodiesLyme borreliosisPhysician-diagnosed erythema migransOnset of illnessVlsE antigenB. burgdorferi infectionBorrelia burgdorferi antigensEnzyme-linked immunosorbentHuman granulocytic ehrlichiosisHuman serumOuter surface protein CRheumatoid arthritisBorrelia burgdorferi sensu strictoOral infectionBurgdorferi infectionFalse-positive reactionsBurgdorferi sensu strictoSera crossLouse-borneLaboratory diagnosisNormal serumGranulocytic ehrlichiosis
2001
Exploitation of Interleukin-8-Induced Neutrophil Chemotaxis by the Agent of Human Granulocytic Ehrlichiosis
Akkoyunlu M, Malawista S, Anguita J, Fikrig E. Exploitation of Interleukin-8-Induced Neutrophil Chemotaxis by the Agent of Human Granulocytic Ehrlichiosis. Infection And Immunity 2001, 69: 5577-5588. PMID: 11500432, PMCID: PMC98672, DOI: 10.1128/iai.69.9.5577-5588.2001.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisInterleukin-8Granulocytic ehrlichiosisHGE bacteriaUpregulation of CXCR2IL-8 receptorsIL-8 productionIL-8 secretionSite of infectionInfected HL-60 cellsObligate intracellular bacteriumChemotaxis chamber assayNeutrophils migrateNeutrophil migrationNeutrophil chemotaxisImmunodeficient miceControl animalsBacterial disseminationHost defensePromyelocytic cell lineChamber assayIntracellular bacteriumHL-60 cellsRetinoic acidNeutrophil lineageRecombinant Protein-44-Based Class-Specific Enzyme-Linked Immunosorbent Assays for Serologic Diagnosis of Human Granulocytic Ehrlichiosis
Magnarelli L, IJdo J, Wu C, Fikrig E. Recombinant Protein-44-Based Class-Specific Enzyme-Linked Immunosorbent Assays for Serologic Diagnosis of Human Granulocytic Ehrlichiosis. European Journal Of Clinical Microbiology & Infectious Diseases 2001, 20: 482-485. PMID: 11561804, DOI: 10.1007/s100960100542.Peer-Reviewed Original ResearchConceptsPolyvalent enzyme-linked immunosorbent assaysClass-specific enzyme-linked immunosorbent assaysEnzyme-linked immunosorbent assayIndirect fluorescent-antibody analysisFluorescent antibody analysisImmunosorbent assaySpecificity testsIgG antibodiesHigh sensitivityHuman granulocytic ehrlichiosisHuman serumGranulocytic ehrlichiosisWhole cell antigenAntibody analysisImmunoglobulin M antibodiesOnset of illnessSerologic diagnosisSerum samplesHuman granulocytic ehrlichiosis (HGE) agentPatient 3False-positive resultsIgM antibodiesM antibodiesTotal immunoglobulinTotal antibodyCoinfection 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 burdenPathogenic strategies of Anaplasma phagocytophilum, a unique bacterium that colonizes neutrophils
Carlyon J, Fikrig E. Pathogenic strategies of Anaplasma phagocytophilum, a unique bacterium that colonizes neutrophils. 2001, 301-330. DOI: 10.1017/cbo9780511754845.014.Peer-Reviewed Original Research
2000
Granulocytic Ehrlichiosis in Mice Deficient in Phagocyte Oxidase or Inducible Nitric Oxide Synthase
Banerjee R, Anguita J, Fikrig E. Granulocytic Ehrlichiosis in Mice Deficient in Phagocyte Oxidase or Inducible Nitric Oxide Synthase. Infection And Immunity 2000, 68: 4361-4362. PMID: 10858261, PMCID: PMC101771, DOI: 10.1128/iai.68.7.4361-4362.2000.Peer-Reviewed Original ResearchSerologic Diagnosis of Lyme Borreliosis by Using Enzyme-Linked Immunosorbent Assays with Recombinant Antigens
Magnarelli L, Ijdo J, Padula S, Flavell R, Fikrig E. Serologic Diagnosis of Lyme Borreliosis by Using Enzyme-Linked Immunosorbent Assays with Recombinant Antigens. Journal Of Clinical Microbiology 2000, 38: 1735-1739. PMID: 10790090, PMCID: PMC86574, DOI: 10.1128/jcm.38.5.1735-1739.2000.Peer-Reviewed Original ResearchConceptsEnzyme-linked immunosorbent assayHuman granulocytic ehrlichiosisRecombinant antigensClass-specific enzyme-linked immunosorbent assaysIgG antibodiesAntibody reactivityLyme borreliosisSerum samplesImmunoblotting of seraImmunoglobulin M antibodiesLow antibody titersB. burgdorferiEnzyme-linked immunosorbentWhole cell antigenAnalysis of serumWestern blot analysisOuter surface protein CErythema migransRheumatoid arthritisAntibody titersIgM antibodiesM antibodiesBorrelia burgdorferi sensu strictoOral infectionSurface protein CCutting Edge: Infection by the Agent of Human Granulocytic Ehrlichiosis Prevents the Respiratory Burst by Down-Regulating gp91phox
Banerjee R, Anguita J, Roos D, Fikrig E. Cutting Edge: Infection by the Agent of Human Granulocytic Ehrlichiosis Prevents the Respiratory Burst by Down-Regulating gp91phox. The Journal Of Immunology 2000, 164: 3946-3949. PMID: 10754283, DOI: 10.4049/jimmunol.164.8.3946.Peer-Reviewed Original ResearchConceptsHGE bacteriaNADPH oxidase enzyme complexHL-60 cellsNADPH oxidaseHuman granulocytic ehrlichiosisEnzyme complexPromyelocytic cell lineTick-borne pathogensInfected cellsCell linesOrganismsMRNA levelsGp91phox proteinRT-PCRDirect inhibitionBacteriaFACS analysisPathogensMRNA expressionOxidaseGenerate superoxide anionCellsRespiratory burstSplenic neutrophilsMicrobesThe Emergence of Another Tickborne Infection in the 12-Town Area around Lyme, Connecticut: Human Granulocytic Ehrlichiosis
IJdo J, Meek J, Cartter M, Magnarelli L, Wu C, Tenuta S, Fikrig E, Ryder R. The Emergence of Another Tickborne Infection in the 12-Town Area around Lyme, Connecticut: Human Granulocytic Ehrlichiosis. The Journal Of Infectious Diseases 2000, 181: 1388-1393. PMID: 10751139, DOI: 10.1086/315389.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisTickborne infectionProspective population-based surveillanceGranulocytic ehrlichiosisCommon tickborne infectionPopulation-based surveillancePrimary care providersSubset of seraIndirect fluorescent antibody methodIllness suggestiveCare providersLaboratory evidenceImportant causeProbable casesFluorescent antibody methodImmunoblot assayLyme diseaseInfectionAntibody methodIncidenceEhrlichiosisLymeMorbidityDiseaseSuggestiveGamma 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
1999
Serodiagnosis of Human Granulocytic Ehrlichiosis by a Recombinant HGE-44-Based Enzyme-Linked Immunosorbent Assay
Ijdo J, Wu C, Magnarelli L, Fikrig E. Serodiagnosis of Human Granulocytic Ehrlichiosis by a Recombinant HGE-44-Based Enzyme-Linked Immunosorbent Assay. Journal Of Clinical Microbiology 1999, 37: 3540-3544. PMID: 10523549, PMCID: PMC85687, DOI: 10.1128/jcm.37.11.3540-3544.1999.Peer-Reviewed Original ResearchConceptsPolyvalent enzyme-linked immunosorbent assaysEnzyme-linked immunosorbent assayRecombinant enzyme-linked immunosorbent assayIndirect fluorescent-antibody assaySerum samplesPatient serum samplesFluorescent-antibody assayCurrent antibodyNormal serum samplesImmunosorbent assayHuman granulocytic ehrlichiosisHuman monocytic ehrlichiosisSuitable antigenHigh costGranulocytic ehrlichiosis
1998
Reactivity of Human Sera to Different Strains of Granulocytic Ehrlichiae in Immunodiagnostic Assays
Magnarelli L, IJdo J, Dumler J, Heimer R, Fikrig E. Reactivity of Human Sera to Different Strains of Granulocytic Ehrlichiae in Immunodiagnostic Assays. The Journal Of Infectious Diseases 1998, 178: 1835-1838. PMID: 9815246, DOI: 10.1086/314516.Peer-Reviewed Original ResearchConceptsNCH-1 strainIndirect IFAHuman granulocytic ehrlichiosis (HGE) agentHuman granulocytic ehrlichiosisWestern blot analysisInfected neutrophilsPromyelocytic leukemia cellsHuman promyelocytic leukemia cellsAntibody detectionGranulocytic ehrlichiosisEhrlichia equiDifferent strainsHuman isolatesLeukemia cellsSerumImmunodiagnostic assaysBlot analysisGranulocytic ehrlichiaeIFA analysisHuman serumIFAEhrlichiaeAssaysSeropositivityPatientsHuman granulocytic ehrlichiosis, a tick-borne disease.
Ijdo JW, Fikrig E. Human granulocytic ehrlichiosis, a tick-borne disease. Nederlands Tijdschrift Voor Geneeskunde 1998, 142: 1778-81. PMID: 9856144.Peer-Reviewed Original ResearchConceptsPresence of leukopeniaRecent tick biteDay of admissionWhite cell countPeripheral blood smearHuman granulocytic ehrlichiosisElevated transaminasesTick-borne diseaseSevere headachePlatelet countTick biteNormal limitsCell countBlood smearsGranulocytic ehrlichiosisDays durationFull recoveryMyalgiaEhrlichiosisHeadacheWeeksLaboratory resultsLaboratory testsDurationCountCloning of the Gene Encoding the 44-Kilodalton Antigen of the Agent of Human Granulocytic Ehrlichiosis and Characterization of the Humoral Response
Ijdo J, Sun W, Zhang Y, Magnarelli L, Fikrig E. Cloning of the Gene Encoding the 44-Kilodalton Antigen of the Agent of Human Granulocytic Ehrlichiosis and Characterization of the Humoral Response. Infection And Immunity 1998, 66: 3264-3269. PMID: 9632594, PMCID: PMC108341, DOI: 10.1128/iai.66.7.3264-3269.1998.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisGranulocytic ehrlichiosisAgent of HGESera of patientsBorrelia burgdorferi infectionMsp-2 genesElicit specific antibodiesHumoral responseBurgdorferi infectionMurine infectionHealthy individualsPatientsSerumSpecific antibodiesHL-60 cellsInfectionAntibodiesEhrlichia chaffeensisAntigenMiceEhrlichiosisGenomic DNA expression libraryMultigene familyGlutathione transferase fusion proteinFusion proteinThe agent of Human Granulocytic Ehrlichiosis resides in an endosomal compartment.
Webster P, IJdo JW, Chicoine LM, Fikrig E. The agent of Human Granulocytic Ehrlichiosis resides in an endosomal compartment. Journal Of Clinical Investigation 1998, 101: 1932-1941. PMID: 9576758, PMCID: PMC508780, DOI: 10.1172/jci1544.Peer-Reviewed Original ResearchConceptsEndocytic pathwayLysosomal membrane glycoproteins lamp-1Membrane-bound compartmentsMannose-6-phosphate receptorInfected host cellsHL-60 cellsEndosomal compartmentsVacuole membraneLAMP-1Host cellsHGE bacteriaVacuolesTransferrin receptorColloidal gold particlesCompartmentsPathwayCytoplasmic vacuolesCellsAgent of HGEReceptorsOrganismsLow pHHuman granulocytic ehrlichiosisBacteriaHGE agent