2014
Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells
Seidman D, Ojogun N, Walker NJ, Mastronunzio J, Kahlon A, Hebert KS, Karandashova S, Miller DP, Tegels BK, Marconi RT, Fikrig E, Borjesson DL, Carlyon JA. Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells. Cellular Microbiology 2014, 16: 1133-1145. PMID: 24612118, PMCID: PMC4115035, DOI: 10.1111/cmi.12286.Peer-Reviewed Original ResearchConceptsGranulocytic anaplasmosisObligate intracellular bacteriumVivo infectionInfectionPhagocytophilum infectionTransmission feedingObligate intracellular pathogensInfected ticksIntracellular pathogensNon-phagocytic cellsIntracellular bacteriumHL-60 cellsHost cell invasionCell invasionAnaplasma phagocytophilumPeptide-specific antiserumOwn uptakeHost cellsAttractive targetInternalization stepMammalian cellsInvasion proteinsSurface proteinsCell morphotypesCells
2012
Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection
Kahlon A, Ojogun N, Ragland SA, Seidman D, Troese MJ, Ottens AK, Mastronunzio JE, Truchan HK, Walker NJ, Borjesson DL, Fikrig E, Carlyon JA. Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection. Infection And Immunity 2012, 81: 65-79. PMID: 23071137, PMCID: PMC3536139, DOI: 10.1128/iai.00932-12.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnaplasma phagocytophilumAnimalsBacterial Outer Membrane ProteinsBinding SitesCell AdhesionCell Line, TumorEhrlichiaEhrlichiosisGene Expression Regulation, BacterialGlutathione TransferaseHL-60 CellsHumansMembrane GlycoproteinsMembrane ProteinsMiceMolecular Sequence DataProtein BindingProtein Structure, TertiaryProteomeSequence Analysis, ProteinTranscription, GeneticUp-RegulationConceptsMammalian host cellsHost cellsReticulate cellsOuter membrane protein candidatesSurface proteinsOuter membrane protein AMembrane protein AA. phagocytophilum-infected ticksObligate intracellular bacteriumA. phagocytophilumGlutathione S-transferaseTranscriptional profilingSurface proteomeC-terminusAffinity purificationFamily AnaplasmataceaeProtein candidatesSelective biotinylationCellular invasionAsp14Transmission feedingAmino acidsS-transferaseIntracellular bacteriumP-selectin glycoprotein ligand-1Anaplasma phagocytophilum Outer Membrane Protein A Interacts with Sialylated Glycoproteins To Promote Infection of Mammalian Host Cells
Ojogun N, Kahlon A, Ragland SA, Troese MJ, Mastronunzio JE, Walker NJ, VieBrock L, Thomas RJ, Borjesson DL, Fikrig E, Carlyon JA. Anaplasma phagocytophilum Outer Membrane Protein A Interacts with Sialylated Glycoproteins To Promote Infection of Mammalian Host Cells. Infection And Immunity 2012, 80: 3748-3760. PMID: 22907813, PMCID: PMC3486060, DOI: 10.1128/iai.00654-12.Peer-Reviewed Original ResearchConceptsMammalian host cellsHuman granulocytic anaplasmosisHost cellsHL-60 cellsA. phagocytophilum organismsExtracellular domainP-selectin glycoprotein-1Outer Membrane Protein ASialylated glycoproteinsA. phagocytophilum infectionA. phagocytophilum-infected ticksN-terminal regionMembrane protein AObligate intracellular bacteriumAmino acids 19HGA patientsPhagocytophilum infectionInfectionTransmission feedingGlutathione S-transferaseGranulocytic anaplasmosisIntracellular bacteriumGlycoprotein 1Anaplasma phagocytophilumA. phagocytophilum
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
c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection
Pedra JH, Mattner J, Tao J, Kerfoot SM, Davis RJ, Flavell RA, Askenase PW, Yin Z, Fikrig E. c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection. Infection And Immunity 2007, 76: 308-316. PMID: 17998313, PMCID: PMC2223674, DOI: 10.1128/iai.00599-07.Peer-Reviewed Original ResearchConceptsIFN-gamma productionA. phagocytophilum infectionPhagocytophilum infectionIFN-gammaJnk2-null miceNatural killer T cellsA. phagocytophilumKiller T cellsIFN-gamma releaseIFN-gamma secretionGamma interferon productionT cell agonistsAnaplasma phagocytophilum infectionT cellsEarly eradicationGamma interferonInterferon productionInfectionC-Jun NH2-terminal kinase-2Inhibitory effectElevated levelsMiceAnaplasma phagocytophilumPhagocytophilumKinase 2ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection
Pedra JH, Sutterwala FS, Sukumaran B, Ogura Y, Qian F, Montgomery RR, Flavell RA, Fikrig E. ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection. The Journal Of Immunology 2007, 179: 4783-4791. PMID: 17878377, DOI: 10.4049/jimmunol.179.7.4783.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnaplasmaAnaplasmosisAnimalsApoptosis Regulatory ProteinsCalcium-Binding ProteinsCaspase 1Disease SusceptibilityEnzyme ActivationHL-60 CellsHumansInterferon-gammaInterleukin-18Killer Cells, NaturalMiceMice, Inbred C57BLMice, KnockoutPhagocytosisSignal TransductionTh1 CellsT-Lymphocytes, RegulatoryConceptsA. phagocytophilum infectionIFN-gamma productionCaspase-1Phagocytophilum infectionIFN-gammaA. phagocytophilumIFN-gamma levelsNOD-like receptor pathwayIL-18 secretionIFN-gamma-mediated controlCentral adaptor moleculeAnaplasma phagocytophilum infectionVitro restimulationIL-18Peripheral bloodControl animalsReceptor pathwayASC deficiencyInfectionObligate intracellular pathogensIntracellular pathogensAnaplasma phagocytophilumPhagocytophilumAdaptor moleculeCritical roleAnaplasma 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
2005
Effects 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 bacteriumAnaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein
Thomas V, Samanta S, Wu C, Berliner N, Fikrig E. Anaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein. Infection And Immunity 2005, 73: 208-218. PMID: 15618156, PMCID: PMC538944, DOI: 10.1128/iai.73.1.208-218.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumDNA-Binding ProteinsGene Expression RegulationHL-60 CellsHomeodomain ProteinsHumansInterferon Regulatory Factor-1Membrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesNuclear ProteinsPhosphoproteinsPhosphorylationPromoter Regions, GeneticProto-Oncogene ProteinsRepressor ProteinsSTAT1 Transcription FactorTrans-ActivatorsTranscription FactorsTranscription, GeneticConceptsCCAAT displacement proteinRegulatory factor 1IRF-1IRF-1 promoterRegulation of genesA. phagocytophilum-infected cellsFirst molecular mechanismFactor 1Interferon regulatory factor 1IFN-gamma signalingActivator proteinGene transcriptionAnaplasma phagocytophilumTranscriptional inhibitionGene expressionMolecular mechanismsNuclear extractsGamma interferon stimulationPhosphorylated STAT1Interferon stimulationGenesA. phagocytophilum infectionProteinProtein expressionReduced expression
2004
Anaplasma 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
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 postinfectionSuperoxide Anion Production during Anaplasma phagocytophila Infection
Wang T, Malawista SE, Pal U, Grey M, Meek J, Akkoyunlu M, Thomas V, Fikrig E. Superoxide Anion Production during Anaplasma phagocytophila Infection. The Journal Of Infectious Diseases 2002, 186: 274-280. PMID: 12134266, DOI: 10.1086/341451.Peer-Reviewed Original ResearchConceptsChronic granulomatous diseaseRespiratory burstA. phagocytophilaRespiratory burst inhibitionNitroblue tetrazoliumPopulation of neutrophilsSuperoxide anion productionInfected miceGranulomatous diseaseMouse modelUse of assaysPolymorphonuclear leukocytesUninfected animalsAnaplasma phagocytophilaAnion productionNeutrophilsInfectionHL-60 cellsIndividual cell basisAssaysCell basisCellsPatientsLeukocytesDisease
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 lineage
2000
Cutting 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 neutrophilsMicrobesGamma 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
1998
Granulocytic Ehrlichiosis in Tick-Immune Guinea Pigs
Das S, Deponte K, Marcantonio N, Ijdo J, Hodzic E, Katavolos P, Barthold S, Telford S, Kantor F, Fikrig E. Granulocytic Ehrlichiosis in Tick-Immune Guinea Pigs. Infection And Immunity 1998, 66: 1803-1805. PMID: 9529119, PMCID: PMC108126, DOI: 10.1128/iai.66.4.1803-1805.1998.Peer-Reviewed Original Research
1997
Immunization against the agent of human granulocytic ehrlichiosis in a murine model.
Sun W, IJdo JW, Telford SR, Hodzic E, Zhang Y, Barthold SW, Fikrig E. Immunization against the agent of human granulocytic ehrlichiosis in a murine model. Journal Of Clinical Investigation 1997, 100: 3014-3018. PMID: 9399947, PMCID: PMC508513, DOI: 10.1172/jci119855.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisGranulocytic ehrlichiosisC3H/HeN miceAgent of HGEMimic human diseaseTick-borne infectionsTransient neutropeniaHeN miceMurine modelPolymorphonuclear leukocytesTick-borne pathogensAoHGEMiceImmunityEhrlichiosisSyringe inoculationHuman diseasesAgentsNeutropeniaImmunizationInfectionLeukocytesDiseaseAntibodiesThe Early Humoral Response in Human Granulocytic Ehrlichiosis
IJdo J, Zhang Y, Hodzic E, Magnarelli L, Wilson M, Telford S, Barthold S, Fikrig E. The Early Humoral Response in Human Granulocytic Ehrlichiosis. The Journal Of Infectious Diseases 1997, 176: 687-692. PMID: 9291316, DOI: 10.1086/514091.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisAntibody responseGranulocytic ehrlichiosisHGE agentC3H/HeJ miceEarly humoral responseEarly antibody responseStrong antibody responseHumoral responseHeJ miceClinical infectionPatientsAntigenHL-60 cellsMiceInfectionIgGEhrlichiosisSerumWeeksResponseIgMAgentsDiseaseDiagnosis