Featured Publications
Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection
Zhu S, Bradfield C, Maminska A, Park E, Kim B, Kumar P, Huang S, Kim M, Zhang Y, Bewersdorf J, MacMicking J. Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection. Science 2024, 383: eabm9903. PMID: 38422126, DOI: 10.1126/science.abm9903.Peer-Reviewed Original ResearchConceptsGuanylate-binding proteinsCaspase-4Surface of Gram-negative bacteriaGuanosine triphosphate hydrolysisImmunity to infectionInnate immunity to infectionCryo-electron tomographyGram-negative bacteriaImmunity proteinSignaling platformsMembrane insertionHuman cellsNative structureCombat infectionsLipopolysaccharide releaseGasdermin DExtended conformationLiving organismsProteinDefense complexCellsNative architectureGBP1BacteriaInfectionA 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 spectrometryCellsMutagenesisGuanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms
Wandel MP, Kim BH, Park ES, Boyle KB, Nayak K, Lagrange B, Herod A, Henry T, Zilbauer M, Rohde J, MacMicking JD, Randow F. Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms. Nature Immunology 2020, 21: 880-891. PMID: 32541830, PMCID: PMC7381384, DOI: 10.1038/s41590-020-0697-2.Peer-Reviewed Original ResearchConceptsGuanylate-binding proteinsCaspase-4 activationCaspase-4Human caspase-4Pyroptotic cell deathGram-negative bacteriaCytosolic bacteriaReplicative nicheEvolutionary evidenceIntracellular bacteriaCell deathMultiple antagonistsNeighboring cellsCaspase-11BacteriaAntibacterial defenseBacterial challengeGasderminShigella flexneriProteinDependent pyroptosisActivationPathwayBacterial lipopolysaccharideGBP2Interferon-induced guanylate-binding proteins in inflammasome activation and host defense
Kim BH, Chee JD, Bradfield CJ, Park ES, Kumar P, MacMicking JD. Interferon-induced guanylate-binding proteins in inflammasome activation and host defense. Nature Immunology 2016, 17: 481-489. PMID: 27092805, PMCID: PMC4961213, DOI: 10.1038/ni.3440.Peer-Reviewed Original ResearchInterferon-inducible effector mechanisms in cell-autonomous immunity
MacMicking JD. Interferon-inducible effector mechanisms in cell-autonomous immunity. Nature Reviews Immunology 2012, 12: 367-382. PMID: 22531325, PMCID: PMC4150610, DOI: 10.1038/nri3210.Peer-Reviewed Original ResearchConceptsCell-autonomous immunityIndividual host cellsHigher organismsVertebrate cellsEffector proteinsIFN-inducible proteinsAutophagic machineryViral life cycleNew proteinsIntracellular distancesGene programMicrobial replicationCapsid assemblyEssential amino acidsMicrobial pathogensHost cellsIntracellular bacteriaIndividual bacteriaKey PointsAtInnate immune systemAmino acidsInterferon familyVariety of mechanismsProteinPathogen classes
2019
Cell-autonomous immunity by IFN-induced GBPs in animals and plants
Huang S, Meng Q, Maminska A, MacMicking JD. Cell-autonomous immunity by IFN-induced GBPs in animals and plants. Current Opinion In Immunology 2019, 60: 71-80. PMID: 31176142, PMCID: PMC6800610, DOI: 10.1016/j.coi.2019.04.017.Peer-Reviewed Original ResearchConceptsGuanylate binding proteinsHost cell interiorCell-autonomous immunitySensory hubMammalian cytosolAnimal kingdomDownstream effectorsDirect bactericidal activityHost cellsBinding proteinCell interiorBacterial pathogensPlantsRecruitment platformDefensive repertoireArabidopsisOrthologuesGTPasesPhytopathogensBacterial colonizationMicrobesCytosolEffectorsProteinColonization