2019
Low ambient humidity impairs barrier function and innate resistance against influenza infection
Kudo E, Song E, Yockey LJ, Rakib T, Wong PW, Homer RJ, Iwasaki A. Low ambient humidity impairs barrier function and innate resistance against influenza infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 10905-10910. PMID: 31085641, PMCID: PMC6561219, DOI: 10.1073/pnas.1902840116.Peer-Reviewed Original ResearchConceptsInfluenza infectionImpair barrier functionImpairs host defenseSeasonal influenza virusesInfluenza virus infectionLungs of miceImpairs mucociliary clearanceTissue repairInduction of IFNInnate antiviral defenseViral burdenMucociliary clearanceDisease outcomeRespiratory challengeVirus infectionSevere diseaseViral infectionCongenic miceHost responseViral transmissionHost defenseSingle-cell RNA sequencingInnate resistanceDisease pathologyInfluenza virus
2016
Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza
2014
An ENU-induced splicing mutation reveals a role for Unc93b1 in early immune cell activation following influenza A H1N1 infection
Lafferty EI, Flaczyk A, Angers I, Homer R, d'Hennezel E, Malo D, Piccirillo CA, Vidal SM, Qureshi ST. An ENU-induced splicing mutation reveals a role for Unc93b1 in early immune cell activation following influenza A H1N1 infection. Genes & Immunity 2014, 15: 320-332. PMID: 24848930, PMCID: PMC4978536, DOI: 10.1038/gene.2014.22.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsCD8-Positive T-LymphocytesChemokine CXCL10EndosomesEthylnitrosoureaImmunity, InnateInfluenza A Virus, H1N1 SubtypeInterferon Type IInterferon-gammaL-SelectinLungLymphocyte ActivationMacrophage ActivationMembrane Transport ProteinsMiceMice, Inbred C57BLMutationOrthomyxoviridae InfectionsToll-Like ReceptorsConceptsEndosomal TLRsImmune responseEndosomal Toll-like receptorsInfluenza A/PR/8/34Expression of CXCL10Toll-like receptorsImmune cell activationCD69 activation markerInnate immune responseHuman infectious diseasesViral clearanceActivation markersInfected lungsRespiratory pathogensTLR responsesT cellsLymphoid cellsCell activationTissue pathologyInfectious diseasesMouse strainsInfectionExudate macrophagesReduced expressionUNC93B1
2011
Airway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway
Mijares LA, Wangdi T, Sokol C, Homer R, Medzhitov R, Kazmierczak BI. Airway Epithelial MyD88 Restores Control of Pseudomonas aeruginosa Murine Infection via an IL-1–Dependent Pathway. The Journal Of Immunology 2011, 186: 7080-7088. PMID: 21572023, PMCID: PMC3110630, DOI: 10.4049/jimmunol.1003687.Peer-Reviewed Original ResearchConceptsInnate immune responseImmune responseMyD88-dependent innate immune responsesIL-1-dependent pathwayBone marrow chimeric miceProtective innate immune responseP. aeruginosaNovel transgenic mouse modelVentilator-associated pneumoniaIL-1R signalingTransgenic mouse modelP. aeruginosa infectionEpithelial cell responsesRadio-resistant cellsIntranasal infectionMyD88 expressionMultiple TLR pathwaysMyD88 functionAeruginosa infectionMouse modelTLR pathwayMurine infectionChimeric miceCell responsesInfectionRIG-like Helicase Innate Immunity Inhibits Vascular Endothelial Growth Factor Tissue Responses via a Type I IFN–dependent Mechanism
Ma B, Dela Cruz CS, Hartl D, Kang MJ, Takyar S, Homer RJ, Lee CG, Elias JA. RIG-like Helicase Innate Immunity Inhibits Vascular Endothelial Growth Factor Tissue Responses via a Type I IFN–dependent Mechanism. American Journal Of Respiratory And Critical Care Medicine 2011, 183: 1322-1335. PMID: 21278304, PMCID: PMC3114061, DOI: 10.1164/rccm.201008-1276oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDEAD Box Protein 58DEAD-box RNA HelicasesDisease Models, AnimalEdemaFocal Adhesion Protein-Tyrosine KinasesImmunity, InnateInflammationInterferon Type IMiceMice, TransgenicMitogen-Activated Protein KinasesNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasePoly I-CPulmonary Disease, Chronic ObstructiveToll-Like Receptor 3Vascular Endothelial Growth Factor AConceptsVascular endothelial growth factorType 2 inflammationChronic obstructive pulmonary disease exacerbationsObstructive pulmonary disease exacerbationsChronic obstructive pulmonary diseaseViral pathogen-associated molecular patternsEndothelial nitric oxide synthaseRIG-like helicasePulmonary disease exacerbationsObstructive pulmonary diseasePathogenesis of asthmaRespiratory syncytial virusNormal pulmonary physiologyNitric oxide synthaseAntiviral innate immunityPathogen-associated molecular patternsReceptor-dependent pathwayTissue responseEndothelial growth factorVEGF receptor 1Ability of VEGFDisease exacerbationPulmonary diseaseRespiratory virusesControl mice
2008
Enhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection
Guillot L, Carroll SF, Homer R, Qureshi ST. Enhanced Innate Immune Responsiveness to Pulmonary Cryptococcus neoformans Infection Is Associated with Resistance to Progressive Infection. Infection And Immunity 2008, 76: 4745-4756. PMID: 18678664, PMCID: PMC2546841, DOI: 10.1128/iai.00341-08.Peer-Reviewed Original ResearchConceptsSJL/J miceKC/CXCL1Cryptococcus neoformans infectionC. neoformans infectionKeratinocyte-derived chemokineNeoformans infectionJ miceInnate immune responseTNF-alphaProgressive infectionImmune responseResistant SJL/J miceMIP-2/CXCL2Pulmonary C. neoformans infectionPulmonary Cryptococcus neoformans infectionPulmonary innate immune responseSJL/J macrophagesC. neoformansInflammatory cytokine tumor necrosis factor alphaEnhanced innate immune responseMIP-1alpha/CCL3IL-12/ILMCP-1/CCL2Cytokine tumor necrosis factor alphaTumor necrosis factor alpha