Featured Publications
A 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 spectrometryCellsMutagenesisA 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-47MtbIFNDiseaseMiceMacrophagesIdentification of nitric oxide synthase as a protective locus against tuberculosis
MacMicking J, North R, LaCourse R, Mudgett J, Shah S, Nathan C. Identification of nitric oxide synthase as a protective locus against tuberculosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 5243-5248. PMID: 9144222, PMCID: PMC24663, DOI: 10.1073/pnas.94.10.5243.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsCarrier ProteinsCation Transport ProteinsCrosses, GeneticDisease SusceptibilityExonsFemaleGenotypeGlucocorticoidsHaplotypesHeterozygoteHomozygoteImmunity, InnateImmunosuppression TherapyIsoenzymesLungMaleMembrane ProteinsMiceMice, Inbred C57BLMice, Inbred StrainsMice, KnockoutMycobacterium tuberculosisNitric Oxide SynthasePolymerase Chain ReactionPolymorphism, GeneticTuberculosisConceptsNitric oxide synthaseOxide synthasePrimary Mycobacterium tuberculosis infectionInducible nitric oxide synthaseHigh-dose glucocorticoidsMycobacterium tuberculosis infectionWild-type miceWild-type littermatesHost immune systemChronic tuberculosisTuberculosis infectionImmune systemCritical host genesTuberculosisMycobacterium tuberculosisProtective genesMiceProtective locusNOS2Host genesSuch pathwaysResponse pathwaysSynthaseGlucocorticoidsLung
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
1998
Identification of Nitric Oxide Synthase 2 as an Innate Resistance Locus against Ectromelia Virus Infection
Karupiah G, Chen J, Nathan C, Mahalingam S, MacMicking J. Identification of Nitric Oxide Synthase 2 as an Innate Resistance Locus against Ectromelia Virus Infection. Journal Of Virology 1998, 72: 7703-7706. PMID: 9696880, PMCID: PMC110049, DOI: 10.1128/jvi.72.9.7703-7706.1998.Peer-Reviewed Original ResearchConceptsNitric oxide synthase 2NOS2-/- miceEctromelia virusCytotoxic T lymphocyte activityEctromelia virus infectionGamma interferon secretionT lymphocyte activityAcute viral infectionSynthase 2Lymphocyte activityNK cellsInterferon secretionVirus infectionImmune responseMonogenic determinantsViral infectionHost survivalCausative agentInfectionMousepoxSecretion