2024
UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling
Harrison A, Yang D, Cahoon J, Geng T, Cao Z, Karginov T, Hu Y, Li X, Chiari C, Qyang Y, Vella A, Fan Z, Vanaja S, Rathinam V, Witczak C, Bogan J, Wang P. UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling. Nature Immunology 2024, 25: 2234-2246. PMID: 39567760, DOI: 10.1038/s41590-024-02004-7.Peer-Reviewed Original Research
2021
STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
Jiao B, An C, Du H, Tran M, Wang P, Zhou D, Wang Y. STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy. Cells 2021, 10: 3057. PMID: 34831280, PMCID: PMC8623460, DOI: 10.3390/cells10113057.Peer-Reviewed Original ResearchConceptsFolic acid nephropathySTAT6 knockout miceM2 macrophage polarizationRenal fibrosis developmentMacrophage polarizationKidney diseaseFibroblast activationKnockout miceRenal fibrosisFibrosis developmentMyeloid fibroblastsEnd-stage kidney diseaseChronic kidney diseaseSevere interstitial fibrosisFibrotic kidney diseaseWild-type miceNovel therapeutic strategiesExtracellular matrix protein productionMatrix protein productionKidney functionPathologic featuresInterstitial fibrosisFibroblast accumulationNephropathyMouse model
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 ResearchMeSH KeywordsAnimalsArthritisChikungunya FeverChikungunya virusImmunity, InnateMembrane ProteinsMiceMice, KnockoutViremiaConceptsVirus 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 deficiencyCXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses
Lin T, Geng T, Harrison AG, Yang D, Vella AT, Fikrig E, Wang P. CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses. Viruses 2020, 12: 1252. PMID: 33147869, PMCID: PMC7692144, DOI: 10.3390/v12111252.Peer-Reviewed Original ResearchConceptsChikungunya virusAlphaviral arthritisArthritogenic alphavirusesLargest immune cell populationMacrophages/T cellsImmune cell populationsInflammatory immune responseLow viral loadWild-type miceO'nyong-nyong virusWild-type animalsRheumatic manifestationsImmune infiltratesViral loadT cellsImmune responseAlphaviral diseaseArthritic diseasesTherapeutic targetCXCL10PathogenesisViral RNACell populationsArthritisFootpadMacrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice
Yang L, Geng T, Yang G, Ma J, Wang L, Ketkar H, Yang D, Lin T, Hwang J, Zhu S, Wang Y, Dai J, You F, Cheng G, Vella AT, Flavell RA, Fikrig E, Wang P. Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice. Communications Biology 2020, 3: 556. PMID: 33033362, PMCID: PMC7545163, DOI: 10.1038/s42003-020-01285-6.Peer-Reviewed Original ResearchConceptsMacrophage scavenger receptor 1Scavenger receptor 1Chikungunya virusReceptor 1Antiviral roleType I IFN responseChikungunya virus infectionLow-density lipoproteinImportant antiviral roleI IFN responseMarkers of autophagyCHIKV infectionViral loadArthritogenic alphavirusesVirus infectionCHIKV replicationATG5-ATG12Antiviral actionKnockout miceMSR1 expressionIFN responseInfectionMiceNsp1 proteinAutophagic function
2019
The GRA15 protein from Toxoplasma gondii enhances host defense responses by activating the interferon stimulator STING
Wang P, Li S, Zhao Y, Zhang B, Li Y, Liu S, Du H, Cao L, Ou M, Ye X, Li P, Gao X, Wang P, Jing C, Shao F, Yang G, You F. The GRA15 protein from Toxoplasma gondii enhances host defense responses by activating the interferon stimulator STING. Journal Of Biological Chemistry 2019, 294: 16494-16508. PMID: 31416833, PMCID: PMC6851339, DOI: 10.1074/jbc.ra119.009172.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalHEK293 CellsHumansImmunity, InnateInterferon-gammaInterleukin-12 Subunit p35Membrane ProteinsMiceMice, Inbred C57BLMice, KnockoutNucleotidyltransferasesProtein MultimerizationProtozoan ProteinsSpleenSurvival RateToxoplasmaToxoplasmosisTumor Necrosis Factor Receptor-Associated Peptides and ProteinsUbiquitinationConceptsImmune responseCyclic GMP-AMP synthaseWT miceRobust innate immune responseCGAS-deficient miceHost immune responseInnate immune responseType I IFNCGAS/STING signalingInterferon-stimulated genesGMP-AMP synthaseInflammatory cytokinesNeurotropic pathogensGRA15Mouse modelSevere symptomsI IFNLatent infectionSTING signalingHigh mortalityMiceInfectionHost defense responsesStingsHost cellsEndogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression
Zhou B, Qi F, Wu F, Nie H, Song Y, Shao L, Han J, Wu Z, Saiyin H, Wei G, Wang P, Ni T, Qian F. Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression. MBio 2019, 10: 10.1128/mbio.00937-19. PMID: 31363026, PMCID: PMC6667616, DOI: 10.1128/mbio.00937-19.Peer-Reviewed Original ResearchConceptsAntiviral immune responseImmune responseInnate immune responseNF-κB subunitsExpression of RelADeficient miceI interferonAntiviral responseVirus-induced cytokine productionHost genome instabilityEndogenous retrovirusesNF-κB signalingType I interferonRNA virus infectionViral RNA mimicViral loadCytokine productionViral challengeVirus infectionLong noncoding RNADeleterious roleRelA expressionViral replicationViral sensorsReduced expressionLack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system
Ketkar H, Yang L, Wormser GP, Wang P. Lack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system. Diagnostic Microbiology And Infectious Disease 2019, 95: 38-40. PMID: 31097261, PMCID: PMC6697611, DOI: 10.1016/j.diagmicrobio.2019.03.012.Peer-Reviewed Original ResearchConceptsZika virus infectionAnti-Zika virus activityVirus infectionAnimal modelsZika virusLethal Zika Virus InfectionIFNAR1 knockout miceZika virus strainLack of efficacyEffectiveness of ivermectinLethal infectionKnockout miceVirus activityAntiviral activityMurine systemVirus strainsDrug ivermectinInfectionIvermectinStudy limitationsPreventionVirusSenegal strainMice
2018
UBXN3B positively regulates STING-mediated antiviral immune responses
Yang L, Wang L, Ketkar H, Ma J, Yang G, Cui S, Geng T, Mordue DG, Fujimoto T, Cheng G, You F, Lin R, Fikrig E, Wang P. UBXN3B positively regulates STING-mediated antiviral immune responses. Nature Communications 2018, 9: 2329. PMID: 29899553, PMCID: PMC5998066, DOI: 10.1038/s41467-018-04759-8.Peer-Reviewed Original ResearchConceptsUbiquitin regulatory X domain-containing proteinAntiviral immune responseImmune responseDeficient immune responseDomain-containing proteinsInterferon genes (STING) signalingVesicular stomatitis virus infectionDiverse biological processesStomatitis virus infectionPhosphorylation of TBK1Physiological evidenceHerpes simplex virus 1Cre-loxP approachSimplex virus 1Virus infectionAdult miceGene signalingHSV-1Biological processesPhysiological functionsVirus 1MicePrimary cellsConsequent recruitmentResponse
2010
Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I
Wang P, Arjona A, Zhang Y, Sultana H, Dai J, Yang L, LeBlanc PM, Doiron K, Saleh M, Fikrig E. Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I. Nature Immunology 2010, 11: 912-919. PMID: 20818395, PMCID: PMC3712356, DOI: 10.1038/ni.1933.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaspase 12Cells, CulturedDEAD Box Protein 58DEAD-box RNA HelicasesDNA-Binding ProteinsFibroblastsImmunity, InnateInterferon Type IMiceMice, Inbred C57BLMice, KnockoutNeuronsReceptors, VirusSignal TransductionTranscription FactorsUbiquitinationUbiquitin-Protein LigasesWest Nile FeverWest Nile virus
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 cytokinesICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System
Dai J, Wang P, Bai F, Town T, Fikrig E. ICAM-1 Participates in the Entry of West Nile Virus into the Central Nervous System. Journal Of Virology 2008, 82: 4164-4168. PMID: 18256150, PMCID: PMC2292986, DOI: 10.1128/jvi.02621-07.Peer-Reviewed Original ResearchConceptsWest Nile virusICAM-1Control animalsWest Nile virus neuroinvasionBlood-brain barrier leakagePathogenesis of encephalitisNile virusBlood-brain barrierLow viral loadWest Nile encephalitisCentral nervous systemICAM-1 participatesVirus neuroinvasionNeuronal damageLeukocyte infiltrationViral encephalitisViral loadBarrier leakageViral infectionNervous systemEncephalitisMiceICAMVirusAnimals