2015
Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers
Walker WE, Kurscheid S, Joshi S, Lopez CA, Goh G, Choi M, Barakat L, Francis J, Fisher A, Kozal M, Zapata H, Shaw A, Lifton R, Sutton RE, Fikrig E. Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers. Journal Of Virology 2015, 89: 5502-5514. PMID: 25740989, PMCID: PMC4442529, DOI: 10.1128/jvi.00118-15.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCase-Control StudiesCD4-Positive T-LymphocytesChemokine CCL3Chemokine CCL4Chemokine CCL5Chemokines, CCCohort StudiesFemaleGene DosageHIV InfectionsHIV Long-Term SurvivorsHIV-1Host-Pathogen InteractionsHumansMacrophage Inflammatory ProteinsMaleMiddle AgedReceptors, CCR5Receptors, CXCR4RNA, MessengerUp-RegulationConceptsElite controllersHIV-seropositive individualsAntiretroviral therapyT cellsMIP-1βMIP-1αHIV infectionSeropositive individualsAbsence of ARTR5-tropic HIV-1Macrophage inflammatory protein-1αR5-tropic HIVInflammatory protein-1αT cell resistancePandemic health problemRANTES chemokinesHIV replicationRare patientsHealthy controlsTherapeutic effectHIV entryHIV-1X4-tropicHealth problemsProtein-1α
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-1Enhanced Survival of Plasmodium-Infected Mosquitoes during Starvation
Zhao YO, Kurscheid S, Zhang Y, Liu L, Zhang L, Loeliger K, Fikrig E. Enhanced Survival of Plasmodium-Infected Mosquitoes during Starvation. PLOS ONE 2012, 7: e40556. PMID: 22808193, PMCID: PMC3393683, DOI: 10.1371/journal.pone.0040556.Peer-Reviewed Original ResearchConceptsSurvival advantageInsulin-like signalingAbility of mosquitoesInsulin-like peptidesInfection altersUninfected mosquitoesOocyst developmentPlasmodium developmentEnhanced expressionInsect vectorsPeriods of starvationFitness costsEnhanced survivalVertebrate hostsMicroarray analysisCarbohydrate catabolismCause malariaPlasmodiumStarvationMosquitoesPostgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice
Mastronunzio JE, Kurscheid S, Fikrig E. Postgenomic Analyses Reveal Development of Infectious Anaplasma phagocytophilum during Transmission from Ticks to Mice. Journal Of Bacteriology 2012, 194: 2238-2247. PMID: 22389475, PMCID: PMC3347074, DOI: 10.1128/jb.06791-11.Peer-Reviewed Original ResearchConceptsOpen reading frameA. phagocytophilum genomeObligate intracellular bacteriaBlood-feeding arthropodsCell surface proteinsMammalian cell cultureRickettsiales orderUncharacterized proteinsRibosomal proteinsEssential proteinsTranscriptome sequencingBacterial adaptationA. phagocytophilumDNA replicationTick salivary glandsPostgenomic analysisReading frameMammalian hostsAnaplasma phagocytophilumDevelopmental transitionsDC-specific markerIntracellular bacteriaTransmission feedingSurface proteinsProtein
2009
The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi
Hovius JW, Bijlsma MF, van der Windt GJ, Wiersinga WJ, Boukens BJ, Coumou J, Oei A, de Beer R, de Vos AF, van 't Veer C, van Dam AP, Wang P, Fikrig E, Levi MM, Roelofs JJ, van der Poll T. The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi. PLOS Pathogens 2009, 5: e1000447. PMID: 19461880, PMCID: PMC2678258, DOI: 10.1371/journal.ppat.1000447.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, InfectiousBorrelia burgdorferiCell MovementHeartHistocytochemistryHumansLeukocytesLyme DiseaseMiceMice, Inbred C57BLMice, KnockoutMyocarditisPhagocytosisReceptors, Urokinase Plasminogen ActivatorSkinStatistics, NonparametricUp-RegulationUrinary BladderUrokinase-Type Plasminogen ActivatorConceptsB. burgdorferi numbersWT controlsPhagocytotic capacityC3H/HeN backgroundIL-1beta mRNA expressionBorrelia burgdorferiB. burgdorferi infectionRole of uPARSevere carditisBurgdorferi infectionImmune responseLeukocyte functionSpirochete Borrelia burgdorferiFibrinolytic systemPAI-1Facilitate clearanceMRNA expressionHuman leukocytesLyme borreliosisMiceB. burgdorferiCausative agentProteinase receptorUPARAdequate eradication
2008
Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain
Wang P, Dai J, Bai F, Kong KF, Wong SJ, Montgomery RR, Madri JA, Fikrig E. Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain. Journal Of Virology 2008, 82: 8978-8985. PMID: 18632868, PMCID: PMC2546894, DOI: 10.1128/jvi.00314-08.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-9Blood-brain barrierWest Nile virusWNV entryMetalloproteinase-9MMP9 expressionWNV infectionIntact blood-brain barrierBlood-brain barrier permeabilityBrain viral loadWest Nile virus entryEvans blue leakageMosquito-borne encephalitisWest Nile encephalitisLethal WNV challengeWild-type miceCentral nervous systemType IV collagen degradationPeripheral viremiaViral loadLeukocyte infiltrateInflammatory cytokinesLikely multifactorialBarrier permeabilityHost cytokinesA Differential Role for BB0365 in the Persistence of Borrelia burgdorferi in Mice and Ticks
Pal U, Dai J, Li X, Neelakanta G, Luo P, Kumar M, Wang P, Yang X, Anderson JF, Fikrig E. A Differential Role for BB0365 in the Persistence of Borrelia burgdorferi in Mice and Ticks. The Journal Of Infectious Diseases 2008, 197: 148-155. PMID: 18171298, DOI: 10.1086/523764.Peer-Reviewed Original ResearchConceptsVertebrate hostsWild-type B. burgdorferiArthropod vectorsB. burgdorferi persistenceB. burgdorferi transcriptomeDiverse murine tissuesSpirochete life cycleLife cycleB. burgdorferi B31Lyme disease agentGene productsMurine tissuesGenesWild rodentsDisease agentsDifferential rolesFeeding ticksB. burgdorferiInfectious isolatesHostBorrelia burgdorferiTicksTranscriptomePersistence of BorreliaMutants
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 pathogens
2004
OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands
Pal U, Yang X, Chen M, Bockenstedt LK, Anderson JF, Flavell RA, Norgard MV, Fikrig E. OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands. Journal Of Clinical Investigation 2004, 113: 220-230. PMID: 14722614, PMCID: PMC311436, DOI: 10.1172/jci19894.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsAntigens, BacterialBacterial Outer Membrane ProteinsBorrelia burgdorferiDisease Models, AnimalEnzyme-Linked Immunosorbent AssayGenetic VectorsImmunoglobulin Fab FragmentsIxodesLipoproteinsLyme DiseaseMiceMice, SCIDMicroscopy, ConfocalModels, GeneticPlasmidsRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionSalivary GlandsSpirochaetalesTime FactorsUp-RegulationConceptsTick salivary glandsWild-type B. burgdorferiArthropod vectorsWild-type spirochetesTransmission of spirochetesB. burgdorferiMajor surface lipoproteinMammalian hostsGene expressionSalivary glandsOspC geneSurface lipoproteinsSalivary gland colonizationInfectious cloneOuter surface protein CGland colonizationSurface protein CTick gutMutantsOspCUnfed ticksInvasionCritical stepBorrelia burgdorferiSpirochetes
2002
Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis
Anguita J, Samanta S, Ananthanarayanan SK, Revilla B, Geba GP, Barthold SW, Fikrig E. Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis. Pathogens And Disease 2002, 34: 187-191. PMID: 12423770, PMCID: PMC4307933, DOI: 10.1111/j.1574-695x.2002.tb00623.x.Peer-Reviewed Original ResearchConceptsJoint inflammationCOX-2B. burgdorferi-specific antibodyBurgdorferi-specific antibodiesOnset of arthritisDegree of inflammationNoninfectious inflammatory diseasesCyclooxygenase-2 activityCOX-2 activityB. burgdorferiCOX-2 gene expressionMurine Lyme arthritisSpecific inhibitionLyme arthritisCytokine responsesInfectious arthritisRheumatoid arthritisInfected miceInflammatory diseasesInducible isoformMurine jointsArthritisInflammationMRNA expressionLyme disease
2000
Inhibition of Th1 Differentiation by IL-6 Is Mediated by SOCS1
Diehl S, Anguita J, Hoffmeyer A, Zapton T, Ihle J, Fikrig E, Rincón M. Inhibition of Th1 Differentiation by IL-6 Is Mediated by SOCS1. Immunity 2000, 13: 805-815. PMID: 11163196, DOI: 10.1016/s1074-7613(00)00078-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsCarrier ProteinsCell DifferentiationDNA-Binding ProteinsGene ExpressionInterferon-gammaInterleukin-12Interleukin-4Interleukin-6MiceReceptors, InterferonRepressor ProteinsSignal TransductionSTAT1 Transcription FactorSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsTh1 CellsTrans-ActivatorsUp-RegulationConceptsIFNgamma gene expressionReceptor-mediated signalsIndependent molecular mechanismsFunctional pleiotropyTranscription 1 (STAT1) phosphorylationNovel functionNegative regulationSignal transducerGene expressionMolecular mechanismsCell differentiationCell typesT cell activationDifferentiationTh2 differentiationTh1 differentiationCell activationNonimmune cellsExpressionTh1 cell differentiationImportant roleCellsInhibitionPleiotropyPhosphorylation