2022
The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
Ryu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022, 55: 1609-1626.e7. PMID: 35963236, PMCID: PMC9474643, DOI: 10.1016/j.immuni.2022.07.007.Peer-Reviewed Original ResearchConceptsToll-like receptor 4ISG inductionMatricellular proteinPro-inflammatory phenotypeAnti-inflammatory macrophagesInterferon-stimulated gene expressionAdipocyte-specific deletionInhibition of glycolysisImmunometabolic adaptationsMyD88 pathwayReceptor 4Chronic diseasesFunctional declineCaloric restrictionInterferon responseHealth spanMacrophagesInflammationMitochondrial respirationSPARCInductionGene expressionAdipokinesObesityIFNInflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1
2019
Monocytes Inadequately Fill In for Meningeal Macrophages
Song E, Iwasaki A. Monocytes Inadequately Fill In for Meningeal Macrophages. Trends In Immunology 2019, 40: 463-465. PMID: 31072686, PMCID: PMC8135183, DOI: 10.1016/j.it.2019.04.004.Peer-Reviewed Original Research
2017
β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares
Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.Peer-Reviewed Original ResearchConceptsKetogenic dietGouty flaresΒ-hydroxybutyrateMajor risk factorAnti-inflammatory moleculesNLRP3-dependent mannerAlternate metabolic fuelsGout flaresJoint destructionIL-1βIntense painInterleukin-1βNLRP3 inflammasomeRisk factorsInflammatory neutrophilsBacterial infectionsNeutrophilsNLRP3Immune defenseGoutMetabolic fuelsBHBS100A9 fibrilsDietPain
2016
CD301b+ Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha
Kumamoto Y, Camporez JP, Jurczak MJ, Shanabrough M, Horvath T, Shulman GI, Iwasaki A. CD301b+ Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha. Immunity 2016, 45: 583-596. PMID: 27566941, PMCID: PMC5033704, DOI: 10.1016/j.immuni.2016.08.002.Peer-Reviewed Original ResearchConceptsMononuclear phagocytesResistin-like molecule αResistin-like molecule alphaSignificant weight lossPositive energy balanceInsulin sensitivityGlucose metabolismAdipose tissueBody weightMultiple organsMultifunctional cytokineBody homeostasisMarked reductionHeterogeneous groupWeight lossPhagocytesMolecule αHomeostasisEnergy balanceRELMαCD301bNormoglycemiaCytokinesMacrophagesCD301b+ Macrophages Are Essential for Effective Skin Wound Healing
Shook B, Xiao E, Kumamoto Y, Iwasaki A, Horsley V. CD301b+ Macrophages Are Essential for Effective Skin Wound Healing. Journal Of Investigative Dermatology 2016, 136: 1885-1891. PMID: 27287183, PMCID: PMC5727894, DOI: 10.1016/j.jid.2016.05.107.Peer-Reviewed Original ResearchConceptsSkin wound healingBarrier functionEssential inflammatory cellsAnti-inflammatory macrophagesWound healingSkin barrier functionSubpopulation of macrophagesEarly regenerative stageMultiple myeloid lineagesInflammatory cellsSyngeneic miceWound healing defectsMyeloid cellsCutaneous repairReparative processesSelective depletionPhenotype switchMacrophagesMyeloid lineageMiceMultiple cell typesHealingCD301bHealing defectsSkin repairAutophagy Snuffs a Macrophage’s Inner Fire
Khoury-Hanold W, Iwasaki A. Autophagy Snuffs a Macrophage’s Inner Fire. Cell Host & Microbe 2016, 19: 9-11. PMID: 26764592, DOI: 10.1016/j.chom.2015.12.015.Peer-Reviewed Original Research
2014
A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells
Iijima N, Iwasaki A. A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells. Science 2014, 346: 93-98. PMID: 25170048, PMCID: PMC4254703, DOI: 10.1126/science.1257530.Peer-Reviewed Original ResearchConceptsMemory lymphocyte clustersMemory T cellsT cellsCD8 tissue-resident memory T cellsTissue-resident memory CD4 T cellsHerpes simplex virus 2 infectionTissue-resident memory T cellsSimplex virus 2 infectionMemory CD4 T cellsEfficient local controlPool of CD4Role of CD4CD4 T cellsVirus 2 infectionVaginal CD4Parabiotic miceGenital mucosaVaccine strategiesChemokine networkLymphocyte clustersHSV-2Viral infectionCD4Local controlInfectionA Promiscuous Lipid-Binding Protein Diversifies the Subcellular Sites of Toll-like Receptor Signal Transduction
Bonham KS, Orzalli MH, Hayashi K, Wolf AI, Glanemann C, Weninger W, Iwasaki A, Knipe DM, Kagan JC. A Promiscuous Lipid-Binding Protein Diversifies the Subcellular Sites of Toll-like Receptor Signal Transduction. Cell 2014, 156: 705-716. PMID: 24529375, PMCID: PMC3951743, DOI: 10.1016/j.cell.2014.01.019.Peer-Reviewed Original ResearchConceptsToll-like receptorsToll-like receptor signal transductionSignal transductionDifferent organellesProinflammatory cytokine expressionSubcellular sitesInnate immune signal transductionInnate immune systemPhosphoinositide-binding domainsImmune signal transductionLipid binding proteinMultiple subcellular locationsReceptor signal transductionCytokine expressionLipid targetsImmune systemInnate immunityHost defenseProtein complexesSubcellular locationPlasma membraneAdaptor TIRAPTIRAPNatural activatorFamily members
2010
Bifurcation of Toll-Like Receptor 9 Signaling by Adaptor Protein 3
Sasai M, Linehan MM, Iwasaki A. Bifurcation of Toll-Like Receptor 9 Signaling by Adaptor Protein 3. Science 2010, 329: 1530-1534. PMID: 20847273, PMCID: PMC3063333, DOI: 10.1126/science.1187029.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3Adaptor Protein Complex beta SubunitsAnimalsCells, CulturedCytokinesCytoplasmic VesiclesDendritic CellsEndosomesInterferon Regulatory Factor-7Interferon Type ILysosomal-Associated Membrane Protein 2MacrophagesMembrane Transport ProteinsMiceMice, Inbred C57BLMyeloid Differentiation Factor 88OligodeoxyribonucleotidesProtein TransportRecombinant Fusion ProteinsSignal TransductionTNF Receptor-Associated Factor 3Toll-Like Receptor 9Transcriptional ActivationVesicle-Associated Membrane Protein 3ConceptsI interferonTLR9 signalsEndosomal Toll-like receptors 7Toll-like receptor 9 signalingToll-like receptor 7Protein 3Type I IFNsDependent proinflammatory cytokinesInterferon regulatory factor 7I IFNsProinflammatory cytokine genesType I interferonNuclear factor κBRegulatory factor 7Viral nucleic acidsProinflammatory cytokinesReceptor 7Factor κBCytokine genesTLR9Adaptor protein 3Intracellular mechanismsFactor 7Viral pathogensReceptor traffickingInfluenza virus activates inflammasomes via its intracellular M2 ion channel
Ichinohe T, Pang IK, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nature Immunology 2010, 11: 404-410. PMID: 20383149, PMCID: PMC2857582, DOI: 10.1038/ni.1861.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCells, CulturedCytokinesDendritic CellsGenetic EngineeringGolgi ApparatusHydrogen-Ion ConcentrationIon ChannelsMacrophagesMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMonensinNLR Family, Pyrin Domain-Containing 3 ProteinOncogene Proteins, ViralOrthomyxoviridaeOrthomyxoviridae InfectionsPotassium ChlorideProtein TransportProtonsSequence DeletionToll-Like Receptor 7Viral Matrix ProteinsVirus Replication
2009
Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling
Tal MC, Sasai M, Lee HK, Yordy B, Shadel GS, Iwasaki A. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 2770-2775. PMID: 19196953, PMCID: PMC2650341, DOI: 10.1073/pnas.0807694106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyAutophagy-Related Protein 5Cells, CulturedDEAD Box Protein 58DEAD-box RNA HelicasesDNA, MitochondrialEnzyme-Linked Immunosorbent AssayFlow CytometryInterferon Type IMacrophagesMiceMicrotubule-Associated ProteinsMitochondriaReactive Oxygen SpeciesReverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsReactive oxygen speciesDysfunctional mitochondriaInnate antiviral defenseAntiviral defenseKey antiviral cytokinesAbsence of autophagyMitochondrial reactive oxygen speciesHomeostatic regulationRole of autophagyTreatment of cellsIPS-1RLR signalingVesicular stomatitis virusAutophagy resultsRNA virusesWT cellsMitochondriaAutophagyType I IFNStomatitis virusRLRLike receptorsOxygen speciesNeurodegenerative diseasesInflammatory disorders
2008
Dendritic cells and macrophages in the genitourinary tract
Iijima N, Thompson J, Iwasaki A. Dendritic cells and macrophages in the genitourinary tract. Mucosal Immunology 2008, 1: 451-459. PMID: 19079212, PMCID: PMC2684461, DOI: 10.1038/mi.2008.57.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsDendritic cellsGenitourinary tractGU tractUnderstanding of DCsSubsets of DCsImmune defenseFemale genital mucosaInnate immune defenseGenital mucosaMaternal toleranceSex hormonesAdaptive immunityReproductive functionMacrophagesTractNumerous agentsSTIsImportant reproductive functionsCellsDivergent rolesMucosaFetusesInfectionHormone
2004
Recognition of single-stranded RNA viruses by Toll-like receptor 7
Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 5598-5603. PMID: 15034168, PMCID: PMC397437, DOI: 10.1073/pnas.0400937101.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationBone Marrow CellsChick EmbryoChloroquineCytokinesDendritic CellsEndosomesInterferon-alphaMacrophagesMembrane GlycoproteinsMiceMice, KnockoutMyeloid Differentiation Factor 88OrthomyxoviridaePeritoneumReceptors, Cell SurfaceReceptors, ImmunologicRhabdoviridae InfectionsRNA, ViralSpleenToll-Like Receptor 7Vesicular stomatitis Indiana virusConceptsVesicular stomatitis virusRNA virusesHigh CpG contentGenomes of virusesToll-like receptorsStomatitis virusMammalian genomesGenomic nucleic acidsAdaptor protein MyD88Endocytic pathwayLigand recognitionCpG contentViral infectionTLR adaptor protein MyD88Innate immune responseToll-like receptor 7Molecular signaturesPlasmacytoid dendritic cellsInnate immune cellsProduction of cytokinesGenomeProtein MyD88Types of pathogensNucleic acidsVivo infection