2020
Sex differences in immune responses that underlie COVID-19 disease outcomes
Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 588: 315-320. PMID: 32846427, PMCID: PMC7725931, DOI: 10.1038/s41586-020-2700-3.Peer-Reviewed Original ResearchConceptsInnate immune cytokinesFemale patientsMale patientsImmune cytokinesDisease outcomeImmune responseCOVID-19COVID-19 disease outcomesPoor T cell responsesSARS-CoV-2 infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusSex-based approachModerate COVID-19Sex differencesRobust T cell activationT cell responsesWorse disease progressionWorse disease outcomesHigher plasma levelsNon-classical monocytesCoronavirus disease 2019T cell activationImmunomodulatory medicationsPlasma cytokinesSARS-CoV-2 infection of the placenta
Hosier H, Farhadian SF, Morotti RA, Deshmukh U, Lu-Culligan A, Campbell KH, Yasumoto Y, Vogels C, Casanovas-Massana A, Vijayakumar P, Geng B, Odio CD, Fournier J, Brito AF, Fauver JR, Liu F, Alpert T, Tal R, Szigeti-Buck K, Perincheri S, Larsen C, Gariepy AM, Aguilar G, Fardelmann KL, Harigopal M, Taylor HS, Pettker CM, Wyllie AL, Dela Cruz CS, Ring AM, Grubaugh ND, Ko AI, Horvath TL, Iwasaki A, Reddy UM, Lipkind HS. SARS-CoV-2 infection of the placenta. Journal Of Clinical Investigation 2020, 130: 4947-4953. PMID: 32573498, PMCID: PMC7456249, DOI: 10.1172/jci139569.Peer-Reviewed Case Reports and Technical NotesMeSH KeywordsAbortion, TherapeuticAbruptio PlacentaeAdultBetacoronavirusCoronavirus InfectionsCOVID-19FemaleHumansMicroscopy, Electron, TransmissionPandemicsPhylogenyPlacentaPneumonia, ViralPre-EclampsiaPregnancyPregnancy Complications, InfectiousPregnancy Trimester, SecondRNA, ViralSARS-CoV-2Viral LoadConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 invasionMaternal antibody responseSymptomatic COVID-19Second trimester pregnancySyndrome coronavirus 2Coronavirus disease 2019Materno-fetal interfaceDense macrophage infiltratesPlacental abruptionSevere preeclampsiaMacrophage infiltratesSevere morbidityTrimester pregnancyPregnant womenCoronavirus 2Antibody responseBackgroundThe effectsDisease 2019Histological examinationImmunohistochemical assaysPlacentaLongitudinal analyses reveal immunological misfiring in severe COVID-19
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.Peer-Reviewed Original ResearchConceptsSevere COVID-19Moderate COVID-19Immune signaturesDisease outcomeCOVID-19Disease trajectoriesInterleukin-5Early immune signaturesInnate cell lineagesType 2 effectorsT cell numbersPoor clinical outcomeWorse disease outcomesImmune response profileCoronavirus disease 2019Distinct disease trajectoriesCytokine levelsImmunological correlatesImmune profileClinical outcomesEarly elevationImmune profilingIL-13Immunoglobulin EDisease 2019
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
2013
Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I
Pang IK, Pillai PS, Iwasaki A. Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 13910-13915. PMID: 23918369, PMCID: PMC3752242, DOI: 10.1073/pnas.1303275110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar Lavage FluidCytokinesDEAD Box Protein 58DEAD-box RNA HelicasesFlow CytometryHistological TechniquesImmunity, InnateImmunohistochemistryInfluenza A virusMembrane GlycoproteinsMiceMice, Inbred C57BLOrthomyxoviridae InfectionsRespiratory Tract InfectionsSignal TransductionToll-Like Receptor 7Viral LoadVirus ReplicationConceptsToll-like receptor 7Innate immune responseRespiratory tractInfected wild-type miceHost innate immune responseAirways of miceViral target cellsWild-type miceAcid-inducible gene 1RIG-I pathwayPattern recognition receptorsHost innate defenseViral replication efficiencyInflammatory mediatorsBronchoalveolar lavageViral loadProinflammatory programProinflammatory responseReceptor 7IAV infectionInflammatory responseVirus infectionLow doseViral replicationVirus replication
2012
A vaccine strategy that protects against genital herpes by establishing local memory T cells
Shin H, Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 2012, 491: 463-467. PMID: 23075848, PMCID: PMC3499630, DOI: 10.1038/nature11522.Peer-Reviewed Original Research
2004
In Vivo Role of Nectin-1 in Entry of Herpes Simplex Virus Type 1 (HSV-1) and HSV-2 through the Vaginal Mucosa
Linehan MM, Richman S, Krummenacher C, Eisenberg RJ, Cohen GH, Iwasaki A. In Vivo Role of Nectin-1 in Entry of Herpes Simplex Virus Type 1 (HSV-1) and HSV-2 through the Vaginal Mucosa. Journal Of Virology 2004, 78: 2530-2536. PMID: 14963155, PMCID: PMC369262, DOI: 10.1128/jvi.78.5.2530-2536.2004.Peer-Reviewed Original ResearchConceptsHSV-2HSV-1Viral entryNectin-1Genital herpesGenital mucosaVaginal epitheliumVaginal mucosaHerpes simplex virus type 2Simplex virus type 2Primary genital herpesHerpes simplex virus type 1Mouse vaginal epitheliumFemale genital tractSimplex virus type 1Virus type 1Virus type 2Intravaginal inoculationHSV infectionMenstrual cycleVaginal infectionsGenital tractMouse modelEstrous cycleType 2