Featured Publications
PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection
Xu D, Jiang W, Wu L, Gaudet R, Park E, Su M, Cheppali S, Cheemarla N, Kumar P, Uchil P, Grover J, Foxman E, Brown C, Stansfeld P, Bewersdorf J, Mothes W, Karatekin E, Wilen C, MacMicking J. PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection. Nature 2023, 619: 819-827. PMID: 37438530, PMCID: PMC10371867, DOI: 10.1038/s41586-023-06322-y.Peer-Reviewed Original ResearchConceptsC-terminal β-barrel domainSpike-mediated fusionCell-autonomous defenseLarge-scale exome sequencingΒ-barrel domainGenome-wide CRISPRSARS-CoV-2 infectionHost cell cytosolScramblase activityPhospholipid scramblaseLive SARS-CoV-2 infectionHuman lung epitheliumPLSCR1SARS-CoV-2 USASingle-molecule switchingSARS-CoV-2 variantsExome sequencingHuman populationRestriction factorsViral RNANew SARS-CoV-2 variantsSARS-CoV-2Robust activityLung epitheliumDefense factorsA human apolipoprotein L with detergent-like activity kills intracellular pathogens
Gaudet RG, Zhu S, Halder A, Kim BH, Bradfield CJ, Huang S, Xu D, Mamiñska A, Nguyen TN, Lazarou M, Karatekin E, Gupta K, MacMicking JD. A human apolipoprotein L with detergent-like activity kills intracellular pathogens. Science 2021, 373 PMID: 34437126, PMCID: PMC8422858, DOI: 10.1126/science.abf8113.Peer-Reviewed Original ResearchMeSH KeywordsApolipoproteins LBacterial Outer MembraneBacteriolysisCell MembraneCell Membrane PermeabilityCells, CulturedCRISPR-Cas SystemsCytosolDetergentsGene EditingGram-Negative BacteriaGTP-Binding ProteinsHumansImmunity, InnateInterferon-gammaLipoproteinsMicrobial ViabilityO AntigensProtein DomainsSalmonella typhimuriumSolubilityConceptsSingle-particle cryo-electron microscopyCell-autonomous defenseCytosol-invasive bacteriaExpression of hundredsNative mass spectrometryCryo-electron microscopyHuman genesDetergent-like activityHost proteinsLipoprotein nanodiscsMammalian lipidsExtracellular transportImmune cytokine interferonCell typesDetergent-like propertiesApolipoprotein LLife-threatening infectionsPotent bactericidal agentsAnionic membranesProteinCytokine interferonNonimmune cellsMass spectrometryCellsMutagenesisInterferon-
Casanova J, MacMicking J, Nathan C. Interferon-. Science 2024, 384: eadl2016. PMID: 38635718, DOI: 10.1126/science.adl2016.Peer-Reviewed Original ResearchGBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals
Shenoy AR, Wellington DA, Kumar P, Kassa H, Booth CJ, Cresswell P, MacMicking JD. GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals. Science 2012, 336: 481-485. PMID: 22461501, DOI: 10.1126/science.1217141.Peer-Reviewed Original ResearchMeSH KeywordsAlum CompoundsAnimalsApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cell LineCytoskeletal ProteinsGTP-Binding ProteinsHumansInflammasomesInterferon-gammaInterleukin-1betaLipopolysaccharidesListeria monocytogenesListeriosisMacrophagesMiceNLR Family, Pyrin Domain-Containing 3 ProteinProtein MultimerizationRNA InterferenceSalmonella typhimuriumUric AcidConceptsGuanylate binding protein 5IL-1β/ILImpaired host defensePresence of infectionNLRP3 inflammasome activationCaspase-1 cleavageNLRP3 inflammasome responseNLRP3 inflammasome assemblyInflammasome assemblyBinding protein 5Inflammatory responseInflammasome activationImmune systemTissue damageInflammasome responseHost defenseInflammasome complexCaspase-1Sensory complexProtein 5InflammasomePathogenic bacteriaILInterleukinNLRA Family of IFN-γ–Inducible 65-kD GTPases Protects Against Bacterial Infection
Kim BH, Shenoy AR, Kumar P, Das R, Tiwari S, MacMicking JD. A Family of IFN-γ–Inducible 65-kD GTPases Protects Against Bacterial Infection. Science 2011, 332: 717-721. PMID: 21551061, DOI: 10.1126/science.1201711.Peer-Reviewed Original ResearchConceptsProtein gene familyCell-autonomous immunityMammalian host defenseHost defense proteinsGene-deficient animalsGene familyAutophagy effectorsDefense proteinsHuman genomeGuanosine triphosphataseHost genesComplete mouseIntracellular bacteriaPhagocyte oxidaseIntracellular pathogensPotent oxidativeAntimicrobial peptidesTrafficking programsHost defenseGenomeFunction analysisFamilyGBP1GenesGBP7Immune Control of Tuberculosis by IFN-γ-Inducible LRG-47
MacMicking JD, Taylor GA, McKinney JD. Immune Control of Tuberculosis by IFN-γ-Inducible LRG-47. Science 2003, 302: 654-659. PMID: 14576437, DOI: 10.1126/science.1088063.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedComputational BiologyDisease SusceptibilityFemaleGTP PhosphohydrolasesGTP-Binding ProteinsHydrogen-Ion ConcentrationImmunity, InnateInterferon-gammaMacrophage ActivationMacrophagesMacrophages, AlveolarMaleMiceMice, Inbred C57BLMutationMycobacterium tuberculosisNitric Oxide SynthaseNitric Oxide Synthase Type IIOligonucleotide Array Sequence AnalysisPhagosomesReverse Transcriptase Polymerase Chain ReactionSignal TransductionTuberculosisConceptsNitric oxide synthase 2LRG-47Principal effector mechanismDefective bacterial killingImmune controlEffector mechanismsMtb replicationImpaired maturationBacterial killingIntracellular pathogensMycobacterium tuberculosisHost macrophagesInfected host macrophagesSynthase 2TuberculosisIRG-47MtbIFNDiseaseMiceMacrophagesInhibition of Viral Replication by Interferon-γ-Induced Nitric Oxide Synthase
Karupiah G, Xie Q, Buller R, Nathan C, Duarte C, MacMicking J. Inhibition of Viral Replication by Interferon-γ-Induced Nitric Oxide Synthase. Science 1993, 261: 1445-1448. PMID: 7690156, DOI: 10.1126/science.7690156.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid OxidoreductasesAnimalsArginineCell LineCells, CulturedEctromelia virusEctromelia, InfectiousEnzyme InductionFemaleHumansInterferon-gammaMacrophagesMiceMice, Inbred C57BLNitric OxideNitric Oxide SynthaseOmega-N-MethylarginineSimplexvirusTransfectionVaccinia virusVirus ReplicationConceptsViral replicationIFN-gammaHerpes simplex-1 virusNitric oxideDetectable NO synthesisSubstantial antiviral effectEctromelia virus infectionNitric oxide synthaseInducible NO synthaseIFN-gamma-treated macrophagesOxide synthaseAntiviral effectVirus infectionNO synthaseNO synthesisAntiviral activityInterferonEpithelial cellsMouse macrophagesCell productionMacrophagesCell typesSynthaseInhibitors
2009
Targeting of the GTPase Irgm1 to the phagosomal membrane via PtdIns(3,4)P2 and PtdIns(3,4,5)P3 promotes immunity to mycobacteria
Tiwari S, Choi HP, Matsuzawa T, Pypaert M, MacMicking JD. Targeting of the GTPase Irgm1 to the phagosomal membrane via PtdIns(3,4)P2 and PtdIns(3,4,5)P3 promotes immunity to mycobacteria. Nature Immunology 2009, 10: 907-917. PMID: 19620982, PMCID: PMC2715447, DOI: 10.1038/ni.1759.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedGTP-Binding ProteinsImmunity, InnateInterferon-gammaIntracellular MembranesLysosomesMacrophagesMiceMycobacterium tuberculosisPhagosomesPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesProtein BindingProtein Structure, SecondaryProtein TransportSignal TransductionSNARE Proteins