2020
A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus
Geng T, Lin T, Yang D, Harrison AG, Vella AT, Fikrig E, Wang P. A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus. The Journal Of Infectious Diseases 2020, 223: 2186-2196. PMID: 33161431, PMCID: PMC8205639, DOI: 10.1093/infdis/jiaa694.Peer-Reviewed Original ResearchConceptsVirus infectionSTING signalingGt miceType I IFN responseChikungunya virus infectionImmune cell infiltrationWild-type miceActivator of neutrophilsInnate immune responseExpression of interferonI IFN responseExpression of chemoattractantsRNA virus infectionDNA virus infectionInterferon genes (STING) pathwayCHIKV arthritisViremic stageArthritis progressionViral burdenArthritis pathogenesisChemokine responsesCell infiltrationJoint damageImmune responseSTING deficiency
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 levelsMosquitoesInnate Immune Responses in the Neutrophils of Community Dwelling and Nursing Home Elders
Juthani-Mehta M, Guo X, Shaw AC, Towle V, Ning Y, Wang X, Allore HG, Fikrig E, Montgomery RR. Innate Immune Responses in the Neutrophils of Community Dwelling and Nursing Home Elders. Journal Of Aging Science 2014, 02 PMID: 25750929, PMCID: PMC4348001, DOI: 10.4172/2329-8847.1000115.Peer-Reviewed Original ResearchNursing home residentsΒ2-integrin expressionToll-like receptorsHome residentsInnate immune responseImmune responseIntegrin CD11bDisabled nursing home residentsIntegrin expressionΒ2 integrin CD11bLevels of chemokinesObservational pilot studyArea nursing homesNursing home eldersLocomotion of neutrophilsTLR4 responseChemokine inductionInfectious disease susceptibilityCommunity dwellingCommunity dwellersNursing homesEfficiency of neutrophilsNeutrophilsUnstimulated neutrophilsFlow cytometry
2013
UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS
Wang P, Yang L, Cheng G, Yang G, Xu Z, You F, Sun Q, Lin R, Fikrig E, Sutton RE. UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS. Cell Reports 2013, 3: 1057-1070. PMID: 23545497, PMCID: PMC3707122, DOI: 10.1016/j.celrep.2013.02.027.Peer-Reviewed Original ResearchConceptsAntiviral immune responseInnate immune responseImmune responseLike receptorsSystemic antiviral immune responsesVirus-induced innate immune responsesDengue virus infectionType I interferon responseI interferon responseRNA virusesVirus infectionViral infectionStrong inhibitory effectViral replicationVirus replicationInterferon responseRNA virus replicationInhibitory effectWest NileMAVSVesicular stomatitisInfectionAdaptor moleculeFamily membersReceptors
2012
Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus
Qian F, Bolen CR, Jing C, Wang X, Zheng W, Zhao H, Fikrig E, Bruce RD, Kleinstein SH, Montgomery RR. Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus. MSphere 2012, 20: 146-155. PMID: 23220997, PMCID: PMC3571267, DOI: 10.1128/cvi.00530-12.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleGene ExpressionGenotypeHepacivirusHepatitis C, ChronicHumansInflammationInterferon-betaInterferonsInterleukinsLeukocytes, MononuclearMacrophagesMalePhosphorylationPolymorphism, Single NucleotideSignal TransductionSTAT1 Transcription FactorToll-Like Receptor 3Tumor Necrosis Factor-alphaViral LoadConceptsToll-like receptor 3Peripheral blood mononuclear cellsHepatitis C virusImmune responseHCV patientsC virusExpression of TLR3Clearance of HCVCommon chronic blood-borne infectionElevated innate immune responseImpaired toll-like receptorPrimary macrophagesHCV genotype 1Ongoing inflammatory responseMajority of patientsBlood-borne infectionsBlood mononuclear cellsToll-like receptorsIFN response genesPotential therapeutic approachInnate immune responseMacrophages of patientsElevated baseline expressionTLR3 pathwayViral clearance
2011
O4-S2.05 Myd-88 deficient mice show evidence of productive T pallidum infection"
Dunne D, Silver A, Fieber J, Zeiss C, Fikrig E. O4-S2.05 Myd-88 deficient mice show evidence of productive T pallidum infection". Sexually Transmitted Infections 2011, 87: a87. DOI: 10.1136/sextrans-2011-050109.149.Peer-Reviewed Original ResearchMyD-88C57BL/6 miceDeficient miceImmunohistochemical stainsImmune responseMurine modelT pallidumDay 10Intact innate immune responseOnly natural reservoirNew Zealand male rabbitsB6 control miceInnate immune cellsUseful murine modelAged C57BL/6 miceWild-type miceInnate immune responseInnate immune systemPattern recognition receptorsImmune response mechanismsDownstream cytokine responsesSyphilis infectionSystemic illnessLymph nodesCytokine responses
2010
Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults
Dunne DW, Shaw A, Bockenstedt LK, Allore HG, Chen S, Malawista SE, Leng L, Mizue Y, Piecychna M, Zhang L, Towle V, Bucala R, Montgomery RR, Fikrig E. Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults. PLOS ONE 2010, 5: e11343. PMID: 20596538, PMCID: PMC2893205, DOI: 10.1371/journal.pone.0011343.Peer-Reviewed Original ResearchConceptsNon-immunosuppressed adultsMIF levelsImmunosuppressive medicationsAutoimmune diseasesIL-8Cytokine productionMonocyte Toll-like receptor (TLR) expressionInnate immunityToll-like receptor expressionEnhanced innate immune responseAltered host immunityAutoimmune disease groupDownstream cytokine productionNon-immunosuppressed individualsUnderlying autoimmune diseaseFeatures of patientsHuman peripheral blood monocytesTLR4 surface expressionCytokine IL-8Number of patientsSurface expressionPeripheral blood monocytesInnate immune responseRisk of infectionImmunosuppressed adultsAge-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response
Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, Allore HG, Montgomery RR, Shaw AC. Age-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response. The Journal Of Immunology 2010, 184: 2518-2527. PMID: 20100933, PMCID: PMC3867271, DOI: 10.4049/jimmunol.0901022.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntibodies, ViralCytokinesDendritic CellsFemaleFlow CytometryHumansInfluenza A Virus, H1N1 SubtypeInfluenza VaccinesInterleukin-12 Subunit p40Interleukin-6Linear ModelsMaleMiddle AgedReverse Transcriptase Polymerase Chain ReactionToll-Like ReceptorsTumor Necrosis Factor-alphaYoung AdultConceptsPrimary human dendritic cellsDendritic cellsHuman dendritic cellsMyeloid DCsPlasmacytoid DCsCytokine productionTLR functionTNF-alphaIntracellular cytokine productionPoor Ab responsesInfluenza vaccine responsesMyeloid dendritic cellsPlasmacytoid dendritic cellsYoung individualsIntracellular cytokine stainingIL-12 productionIFN-alpha productionTLR ligand stimulationTLR gene expressionInnate immune responseAge-Associated DecreaseTLR8 engagementInfluenza immunizationAge-associated effectsCytokine staining
2009
Human innate immunosenescence: causes and consequences for immunity in old age
Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC. Human innate immunosenescence: causes and consequences for immunity in old age. Trends In Immunology 2009, 30: 325-333. PMID: 19541535, PMCID: PMC4067971, DOI: 10.1016/j.it.2009.05.004.Peer-Reviewed Original ResearchConceptsInnate immune system initiatesNatural killer T cellsOlder ageAntiviral cytokine productionKiller T cellsInnate immune responseInnate immune systemDendritic cellsNatural killerCytokine productionHuman immunosenescenceT cellsImmune responseAdaptive immunityImmune systemInnate immunityImmunityAgeCellsDiverse cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfectionInnate 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
2008
Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly
Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE, Fikrig E, Montgomery RR. Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly. Journal Of Virology 2008, 82: 7613-7623. PMID: 18508883, PMCID: PMC2493309, DOI: 10.1128/jvi.00618-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overCell Adhesion MoleculesCell LineCells, CulturedCytokinesFemaleHumansImmunity, InnateLectins, C-TypeMacrophagesMaleMiddle AgedNorth AmericaProtein BindingReceptors, Cell SurfaceSTAT1 Transcription FactorToll-Like Receptor 3Viral Envelope ProteinsWest Nile FeverWest Nile virusConceptsInnate immune responseToll-like receptor 3Intercellular adhesion molecule 3West Nile virusImmune responseYoung donorsC-type lectin dendritic cell-specific intercellular adhesion molecule 3Dendritic cell-specific intercellular adhesion molecule 3Nile virusBlood-brain barrierWNV envelope proteinSevere neurological diseaseResponsiveness of macrophagesPrimary human macrophagesCytokine levelsOlder donorsWNV infectionNeurological diseasesReceptor 3Human macrophagesOlder individualsElevated levelsMacrophagesMolecule 3Significant differences
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 protein
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
1999
Selective Anti-Inflammatory Action of Interleukin-11 in Murine Lyme Disease: Arthritis Decreases while Carditis Persists
Anguita J, Barthold S, Samanta S, Ryan J, Fikrig E. Selective Anti-Inflammatory Action of Interleukin-11 in Murine Lyme Disease: Arthritis Decreases while Carditis Persists. The Journal Of Infectious Diseases 1999, 179: 734-737. PMID: 9952389, DOI: 10.1086/314613.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsAntibodies, MonoclonalArthritis, InfectiousFemaleHumansInflammationInterferon-gammaInterleukin-11Interleukin-12Interleukin-4Lyme DiseaseMiceMice, Inbred C3HMyocarditisNitric Oxide SynthaseNitric Oxide Synthase Type IIRecombinant ProteinsRNA, MessengerTranscription, GeneticConceptsMurine Lyme diseaseIL-11Potent anti-inflammatory propertiesInducible nitric oxide synthaseLyme diseaseMurine Lyme carditisAnti-inflammatory actionRole of interleukinAnti-inflammatory propertiesNitric oxide synthaseInnate immune responseB. burgdorferi-infected miceBurgdorferi-infected miceLyme carditisCardiac inflammationLyme arthritisIL-12Less arthritisIL-4Oxide synthaseBlocking antibodiesImmune responseControl animalsInterleukin-11Borrelia burgdorferi