2023
Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development
Rana V, Kitsou C, Dutta S, Ronzetti M, Zhang M, Bernard Q, Smith A, Tomás-Cortázar J, Yang X, Wu M, Kepple O, Li W, Dwyer J, Matias J, Baljinnyam B, Oliver J, Rajeevan N, Pedra J, Narasimhan S, Wang Y, Munderloh U, Fikrig E, Simeonov A, Anguita J, Pal U. Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development. Science 2023, 379: eabl3837. PMID: 36634189, PMCID: PMC10122270, DOI: 10.1126/science.abl3837.Peer-Reviewed Original ResearchConceptsBlood meal acquisitionMetazoan developmentTick receptorArthropod immunityMammalian hostsSignaling pathwaysReceptor motifEvolutionary dependenceVectorial competenceStem cellsCommunication pathwaysPathwayCritical roleVector immunityHostHigh affinityGenomeAntimicrobial componentsHedgehogJAKMotifMetamorphosisImmunityParasitesPhysiology
2020
Interactions Between Ticks and Lyme Disease Spirochetes.
Pal U, Kitsou C, Drecktrah D, Yaş ÖB, Fikrig E. Interactions Between Ticks and Lyme Disease Spirochetes. Current Issues In Molecular Biology 2020, 42: 113-144. PMID: 33289683, PMCID: PMC8045411, DOI: 10.21775/cimb.042.113.Peer-Reviewed Original ResearchConceptsComplex enzootic life cycleEnzootic life cycleMammalian reservoir hostsMolecular interactionsLife cycleDiscrete molecular interactionsVariety of animalsRelated ticksVertebrate hostsLyme disease spirocheteArthropod vectorsSensu latoPathogen persistenceWild rodentsBacterial pathogensReservoir hostsCritical roleTick-transmitted infectionsMain vectorNortheastern United StatesPast discoveriesHostTicksArthropodsSpirochetes
2018
MiR-221 negatively regulates innate anti-viral response
Du H, Cui S, Li Y, Yang G, Wang P, Fikrig E, You F. MiR-221 negatively regulates innate anti-viral response. PLOS ONE 2018, 13: e0200385. PMID: 30089112, PMCID: PMC6082502, DOI: 10.1371/journal.pone.0200385.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntagomirsDNA-Binding ProteinsDown-RegulationHEK293 CellsHerpesvirus 1, HumanHumansImmunity, InnateInterferon-betaMacrophagesMiceMice, Inbred C57BLMice, KnockoutMicroRNAsPromoter Regions, GeneticProtein Serine-Threonine KinasesRhabdoviridae InfectionsTranscription FactorsVesiculovirusConceptsAntiviral responseMiR-221Innate anti-viral responseInitial antiviral responseImmune cell activationMiR-221 expressionAnti-viral responseInnate antiviral responseInnate immune systemAnti-viral defenseIFNβ productionVirus infectionMultiple candidate targetsImmune systemCell activationCandidate targetsInfectionRNA-seq analysisCritical roleDirect bindingResponseMicroRNA regulators
2014
Innexin AGAP001476 Is Critical for Mediating Anti-Plasmodium Responses in Anopheles Mosquitoes
Li MW, Wang J, Zhao YO, Fikrig E. Innexin AGAP001476 Is Critical for Mediating Anti-Plasmodium Responses in Anopheles Mosquitoes. Journal Of Biological Chemistry 2014, 289: 24885-24897. PMID: 25035430, PMCID: PMC4155657, DOI: 10.1074/jbc.m114.554519.Peer-Reviewed Original ResearchConceptsAnti-Plasmodium responseToll pathwayInnate immune responseGap junction proteinIMD pathwaySignal transductionExtracellular communicationSimultaneous knockdownAnopheles gambiaeImmune responseMidgut epitheliumInhibitor studiesKnockdownPlasmodium falciparum infectionCactusBlood mealGap junctionsVitellogenin levelsOocyst numbersAnopheles mosquitoesJunction proteinsCritical rolePathwayMRNA levelsMosquitoes
2013
Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis
Qian F, Chung L, Zheng W, Bruno V, Alexander RP, Wang Z, Wang X, Kurscheid S, Zhao H, Fikrig E, Gerstein M, Snyder M, Montgomery RR. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses 2013, 5: 1664-1681. PMID: 23881275, PMCID: PMC3738954, DOI: 10.3390/v5071664.Peer-Reviewed Original ResearchConceptsCommon gene pathwaysNovel cellular responsesDifferential gene expressionRNA-seq analysisWest Nile virusGene expression analysisPrimary human macrophagesGene isoformsHigh-throughput methodRNA-seqGene pathwaysExpression analysisGenes CriticalKnock-downGene expressionCellular responsesGene changesResistant individualsBiological settingsHuman macrophagesGenesCritical roleAvailable treatmentsHealthy donorsViral infection
2012
Ixodes 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
2007
ASC/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 TransductionT-Lymphocytes, RegulatoryTh1 CellsConceptsA. 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 roleA Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector
Narasimhan S, Sukumaran B, Bozdogan U, Thomas V, Liang X, DePonte K, Marcantonio N, Koski RA, Anderson JF, Kantor F, Fikrig E. A Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector. Cell Host & Microbe 2007, 2: 7-18. PMID: 18005713, PMCID: PMC2699493, DOI: 10.1016/j.chom.2007.06.001.Peer-Reviewed Original ResearchConceptsMammalian hostsComplex feeding sitesLyme disease agent Borrelia burgdorferiSuccessful migrationMammalian responseTick Ixodes scapularisTick salivary glandsReactive oxygen speciesFeeding sitesArthropod vectorsTick proteinsBurgdorferi-infected miceOxygen speciesEfficient vectorCritical roleSpirochete acquisitionIxodes scapularisB. burgdorferiPathogensHostBorrelia burgdorferiI. scapularisInflammatory cellsImmune cellsSurvival advantage
2003
STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity
Welte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE, Bothwell AL, Fikrig E, Koni PA, Flavell RA, Fu XY. STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 1879-1884. PMID: 12571365, PMCID: PMC149927, DOI: 10.1073/pnas.0237137100.Peer-Reviewed Original ResearchConceptsDeletion of Stat3STAT3 deletionInnate immune responseKey transcriptional mediatorNormal embryonic developmentCell-autonomous proliferationAbsence of STAT3Tissue-specific disruptionImmune responseInnate immunityCritical roleTumor necrosis factor alphaNF-kappa B activationTranscriptional mediatorsEmbryonic developmentBowel wall thickeningHematopoiesis resultsInflammatory cell infiltrationSignal transducerNecrosis factor alphaTranscription 3NAPDH oxidase activityBone marrow cellsMyeloid lineageSTAT3