2020
Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. PLOS Neglected Tropical Diseases 2020, 14: e0008112. PMID: 32150565, PMCID: PMC7082063, DOI: 10.1371/journal.pntd.0008112.Peer-Reviewed Original ResearchConceptsZika virusCell subsetsDengue virusConcurrent dengue infectionInnate cell responsesInnate immune signaturesVirus-infected individualsDivergent clinical outcomesMosquito-borne human pathogenIntact immune responsePre-existing infectionInnate cell typesSingle-cell immune profilingPublic health importanceCell typesImmune signaturesVirus patientsWest Nile virusAcute patientsClinical outcomesImmune profilingDengue infectionImmune statusFunctional statusImmune cells
2019
Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils
Hastings AK, Uraki R, Gaitsch H, Dhaliwal K, Stanley S, Sproch H, Williamson E, MacNeil T, Marin-Lopez A, Hwang J, Wang Y, Grover JR, Fikrig E. Aedes aegypti NeSt1 Protein Enhances Zika Virus Pathogenesis by Activating Neutrophils. Journal Of Virology 2019, 93: 10.1128/jvi.00395-19. PMID: 30971475, PMCID: PMC6580965, DOI: 10.1128/jvi.00395-19.Peer-Reviewed Original ResearchConceptsVirus infectionBite siteMosquito salivaImmune cellsZika virusLocal immune environmentMosquito bite siteZika virus pathogenesisEarly viral replicationZika virus infectionFactor 1Pathogenesis of flavivirusesVirus-infected mosquitoesVirus-induced pathogenesisCXCL2 expressionImmune environmentPassive immunizationZIKV pathogenesisImmune microenvironmentAntibody responseZIKV replicationVirus pathogenesisMosquito bitesPrimary mouse neutrophilsImmune system
2018
Circadian Rhythms Influence the Severity of Sepsis in Mice via a TLR2-Dependent, Leukocyte-Intrinsic Mechanism
Heipertz EL, Harper J, Lopez CA, Fikrig E, Hughes ME, Walker WE. Circadian Rhythms Influence the Severity of Sepsis in Mice via a TLR2-Dependent, Leukocyte-Intrinsic Mechanism. The Journal Of Immunology 2018, 201: ji1701677. PMID: 29760192, PMCID: PMC9351006, DOI: 10.4049/jimmunol.1701677.Peer-Reviewed Original ResearchConceptsImmune cellsZT 19C57BL/6 miceWorse outcomesTLR2 agonist lipoteichoic acidCircadian rhythmTLR2 knockout miceFemale C57BL/6 miceMale C57BL/6 miceSeverity of sepsisBone marrow chimerasTLR2-dependent mechanismIL-6 productionTLR2-DependentSepsis severityCecal ligationSepsis phenotypesSepsisC57BL/6 cellsSimilar outcomesMiceMouse cecumLipoteichoic acidMurine macrophagesCLPDaily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells
Silver AC, Buckley SM, Hughes ME, Hastings AK, Nitabach MN, Fikrig E. Daily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells. Heliyon 2018, 4: e00579. PMID: 29862343, PMCID: PMC5968137, DOI: 10.1016/j.heliyon.2018.e00579.Peer-Reviewed Original ResearchAdherent splenocytesToll-like receptor expressionMRNA levelsProtein levelsSplenic immune cellsToll-like receptorsDependent immune responsesZeitgeber time (ZT) 1Adherent cell populationDendritic cellsTLR3 ligandTLR ligandsCytokine expressionSplenocyte populationImmune cellsReceptor expressionImmune responseSplenic macrophagesB cellsRhythmic expressionCell populationsTLRSplenocytesDaily light-dark cycleCircadian rhythm
2011
Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells
Silver AC, Arjona A, Hughes ME, Nitabach MN, Fikrig E. Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells. Brain Behavior And Immunity 2011, 26: 407-413. PMID: 22019350, PMCID: PMC3336152, DOI: 10.1016/j.bbi.2011.10.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsARNTL Transcription FactorsB-LymphocytesCircadian RhythmCircadian Rhythm Signaling Peptides and ProteinsCLOCK ProteinsDendritic CellsDNA-Binding ProteinsGene ExpressionMacrophagesMiceNuclear Receptor Subfamily 1, Group D, Member 1Period Circadian ProteinsPhotoperiodSpleenTranscription FactorsConceptsMolecular clock mechanismClock genesClock mechanismGene expressionClock-controlled transcription factorsFunctional molecular clockAspects of physiologyConstant environmental conditionsMolecular clockTranscription factorsCircadian expressionB cellsEnvironmental conditionsLight-dark cycleMouse macrophagesDaily rhythmsGenesExpressionCellsDendritic cellsMurine spleenMammalsMacrophagesSplenic NK cellsImmune cellsInnate interleukin-22 confers protection during acute liver infection (114.8)
Zenewicz L, Pedra J, Booth C, Fikrig E, Flavell R. Innate interleukin-22 confers protection during acute liver infection (114.8). The Journal Of Immunology 2011, 186: 114.8-114.8. DOI: 10.4049/jimmunol.186.supp.114.8.Peer-Reviewed Original ResearchLTi-like cellsIL-22Liver infectionLiver immune responseObligate intracellular bacterium Anaplasma phagocytophilumInnate immune cellsLymphoid tissue inducerIL-22 receptorRole of innateIL-22-dependent mannerTissue responseImportant protective roleBacterium Anaplasma phagocytophilumA. phagocytophilum infectionIL-23Liver injuryImmune cellsLymphoid tissueInterleukin-22Immune responseGastrointestinal tractImportant cytokineConfer protectionProtective roleBacterial infections
2009
Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing
Town T, Bai F, Wang T, Kaplan AT, Qian F, Montgomery RR, Anderson JF, Flavell RA, Fikrig E. Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing. Immunity 2009, 30: 242-253. PMID: 19200759, PMCID: PMC2707901, DOI: 10.1016/j.immuni.2008.11.012.Peer-Reviewed Original ResearchConceptsToll-like receptor 7West Nile virusReceptor 7WNV infectionImmune cell infiltrationLethal WNV infectionMyeloid differentiation factorIL-23 p19IL-23 responsesIL-12 p40West Nile encephalitisIL-12 p35Infected target cellsHost defense mechanismsRNA flavivirusInnate cytokinesWNV encephalitisInterleukin-12Cell infiltrationImmune cellsTarget organsVariable severityMiceTarget cellsTissue concentrationsInnate Immune Responses to West Nile Virus Infection
Arjona A, Fikrig E. Innate Immune Responses to West Nile Virus Infection. Emerging Infectious Diseases Of The 21st Century 2009, 169-187. DOI: 10.1007/978-0-387-79840-0_8.Peer-Reviewed Original ResearchWest Nile virus infectionPathogen recognition receptorsImmune cellsVirus infectionImmune responseBlood-brain barrier permeabilityInnate immune cellsAdaptive immune responsesInnate immune mechanismsInnate immune responseInnate antiviral immunityWNV neuroinvasionProinflammatory cytokinesCostimulatory moleculesImmune mechanismsBarrier permeabilityAntiviral immunityWNV infectionInnate responseAntiviral stateInfectionCytokinesDetrimental effectsCurrent understandingImmunopathogenesis
2007
West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses
Arjona A, Ledizet M, Anthony K, Bonafé N, Modis Y, Town T, Fikrig E. West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses. The Journal Of Immunology 2007, 179: 8403-8409. PMID: 18056386, DOI: 10.4049/jimmunol.179.12.8403.Peer-Reviewed Original ResearchConceptsWest Nile virusInnate immune responseReceptor-interacting protein 1Immune responseMajor structural proteinVirus-associated molecular patternsDipteran cellsViral replication intermediatesRNA helicasesAdaptor molecule TRIFReplication intermediatesStructural proteinsWNV envelope proteinGlycosylation patternsMolecular patternsAntiviral stateGlycosylation profileProtein 1Murine macrophagesProinflammatory cytokinesCytokine productionImmunosuppressive effectsDsRNAImmune cellsEnvelope proteinA 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