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
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 diseasesAnaplasma 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. phagocytophilumIxodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis
Liu L, Dai J, Zhao YO, Narasimhan S, Yang Y, Zhang L, Fikrig E. Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis. The Journal Of Infectious Diseases 2012, 206: 1233-1241. PMID: 22859824, PMCID: PMC3448968, DOI: 10.1093/infdis/jis484.Peer-Reviewed Original ResearchConceptsJAK-STAT pathwayTick salivary glandsA. phagocytophilum infectionAntimicrobial peptidesElectrophoretic mobility shift assaysPeptide-encoding genesMobility shift assaysPhagocytophilum infectionHuman granulocytic anaplasmosisGene familyTransducer activatorMammalian hostsRNA interferenceShift assaysTranscription pathwayGene expressionJAK-STATJanus kinaseGranulocytic anaplasmosisSalivary glandsPathwayGenesCritical roleAnaplasma phagocytophilumKey role
2011
Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands
Liu L, Narasimhan S, Dai J, Zhang L, Cheng G, Fikrig E. Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands. EMBO Reports 2011, 12: 1196-1203. PMID: 21921936, PMCID: PMC3207102, DOI: 10.1038/embor.2011.177.Peer-Reviewed Original ResearchConceptsA. phagocytophilum infectionSalivary glandsA. phagocytophilumPhagocytophilum infectionAnaplasma phagocytophilumTick gutA. phagocytophilum-infected mice
2010
Anaplasma 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
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
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
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
2003
Murine 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