2023
Early cellular and molecular signatures correlate with severity of West Nile virus infection
Lee H, Zhao Y, Fleming I, Mehta S, Wang X, Vander Wyk B, Ronca S, Kang H, Chou C, Fatou B, Smolen K, Levy O, Clish C, Xavier R, Steen H, Hafler D, Love J, Shalek A, Guan L, Murray K, Kleinstein S, Montgomery R. Early cellular and molecular signatures correlate with severity of West Nile virus infection. IScience 2023, 26: 108387. PMID: 38047068, PMCID: PMC10692672, DOI: 10.1016/j.isci.2023.108387.Peer-Reviewed Original ResearchWest Nile virusEffective anti-viral responseInnate immune cell typesWest Nile virus infectionPro-inflammatory markersAcute time pointsImmune cell typesAnti-viral responseMolecular signaturesHost cellular activitiesAcute infectionAsymptomatic donorsPeripheral bloodSevere infectionsVirus infectionImmune responseSevere casesCell activityIll individualsSerum proteomicsInfectionInfection severityHigh expressionTime pointsNile virusPD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2019
Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserum
2018
Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV
Farhadian SF, Mehta SS, Zografou C, Robertson K, Price RW, Pappalardo J, Chiarella J, Hafler DA, Spudich SS. Single-cell RNA sequencing reveals microglia-like cells in cerebrospinal fluid during virologically suppressed HIV. JCI Insight 2018, 3: e121718. PMID: 30232286, PMCID: PMC6237230, DOI: 10.1172/jci.insight.121718.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionImmune activationAntiretroviral therapyNeuronal injuryCentral nervous system immune activationLong-term suppressive antiretroviral therapySingle-cell RNA sequencingCNS immune activationDisease-associated microgliaSuppressive antiretroviral therapyImmune cell subsetsMicroglia-like cellsGene expression signaturesNeuronal damageNeuroinflammatory diseasesRNA sequencingCell subsetsCNS cellsNeurological conditionsRare subsetNeurocognitive impairmentMyeloid cellsCellular subsetsInfection
2014
TLR7 induces anergy in human CD4+ T cells
Dominguez-Villar M, Gautron AS, de Marcken M, Keller MJ, Hafler DA. TLR7 induces anergy in human CD4+ T cells. Nature Immunology 2014, 16: 118-128. PMID: 25401424, PMCID: PMC4413902, DOI: 10.1038/ni.3036.Peer-Reviewed Original ResearchSystems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cells
2011
An Innate Role for IL-17
Dominguez-Villar M, Hafler DA. An Innate Role for IL-17. Science 2011, 332: 47-48. PMID: 21454778, DOI: 10.1126/science.1205311.Peer-Reviewed Original ResearchConceptsImmune responseImmune dysregulation polyendocrinopathyAbnormal immune responseRegulatory immune cellsRegulatory T cellsHuman autoimmune disordersCytokine interleukin-17Normal immune responseTranscription factor Foxp3IL-17Interleukin-17Autoimmune disordersAutoimmune diseasesImmune cellsImmune system processFOXP3 geneFactor Foxp3T cellsImmune systemFungal infectionsGenetic mutationsHuman genetic mutationsCytokinesInfectionCell types
2008
TIMs: central regulators of immune responses
Hafler DA, Kuchroo V. TIMs: central regulators of immune responses. Journal Of Experimental Medicine 2008, 205: 2699-2701. PMID: 19015312, PMCID: PMC2585854, DOI: 10.1084/jem.20082429.Peer-Reviewed Original ResearchConceptsExhausted T cellsT cell exhaustionHIV infectionPD-1T cellsCell exhaustionMucin domain-containing protein 3Chronic HIV infectionChronic viral infectionsHuman HIV infectionT cell responsesChronic viral diseasesT-cell immunoglobulinDomain-containing protein 3Novel therapeutic targetTim-3Opportunistic infectionsCell immunoglobulinImmune responseTherapeutic targetViral infectionCell responsesProtein 3InfectionViral diseases
2001
Immune Tolerance and the Nervous System
Anderson D, Hafler D. Immune Tolerance and the Nervous System. Advances In Experimental Medicine And Biology 2001, 490: 79-98. PMID: 11505978, DOI: 10.1007/978-1-4615-1243-1_9.Peer-Reviewed Original ResearchConceptsT cellsB cellsInnate immunityForeign microbial antigensPrior viral infectionSpecific immune responseClass I moleculesNK cellsImmune toleranceMicrobial antigensImmune responseViral infectionNervous systemInfectious agentsSecondary exposureImmune systemInfectious virusParticular antigenSpecific receptorsTumor cellsAntigenI moleculesInfectionInnate mechanismsImmunity
1994
Human T cell lymphotropic virus type I-induced T cell activation. Resistance to TGF-beta 1-induced suppression.
Höllsberg P, Ausubel LJ, Hafler DA. Human T cell lymphotropic virus type I-induced T cell activation. Resistance to TGF-beta 1-induced suppression. The Journal Of Immunology 1994, 153: 566-73. PMID: 8021495, DOI: 10.4049/jimmunol.153.2.566.Peer-Reviewed Original ResearchConceptsT cell clonesT cell activationHuman T-cell lymphotropic virus type ILymphotropic virus type IVirus type ICell activationCell clonesT cellsCD3/TCR complexHTLV-I myelopathyT cell proliferationType IImmune regulationHTLVHyperphosphorylation of pRbProductive infectionCell cycle progressionCell proliferationTCR complexPatientsG1 phaseInfectionSingle cell cloningCycle progressionActivation
1989
Sequestration of virus-specific T cells in the cerebrospinal fluid of a patient with varicella zoster viral meningoencephalitis
Duby A, Weiner H, Benjamin D, Seidman JG, Hafler D. Sequestration of virus-specific T cells in the cerebrospinal fluid of a patient with varicella zoster viral meningoencephalitis. Journal Of Neuroimmunology 1989, 22: 63-68. PMID: 2465314, DOI: 10.1016/0165-5728(89)90010-6.Peer-Reviewed Original ResearchConceptsT cell clonesVirus-specific T cellsT cellsCerebrospinal fluidViral meningoencephalitisImmune responseViral infectionHerpes zoster viral infectionAntigen-specific T cellsT-cell receptor beta-chain gene rearrangementBeta-chain gene rearrangementsT cell responsesPatient's cerebrospinal fluidSecondary immune responseT-cell antigen receptor beta-chain geneBeta-chain geneMyelin basic proteinVZV meningoencephalitisMumps virusMeningoencephalitisPatientsClonal expansionGene rearrangementsBlot analysisInfection
1987
Secondary immune amplification following live poliovirus immunization in humans
Hafler D, Fox D, Benjamin D, Blue M, Weiner H. Secondary immune amplification following live poliovirus immunization in humans. Clinical Immunology 1987, 44: 321-328. PMID: 3040309, DOI: 10.1016/0090-1229(87)90076-6.Peer-Reviewed Original ResearchConceptsAutologous mixed lymphocyte responseRecall antigensAnamnestic responseImmune amplificationImmune responseHuman T cell responsesT cell proliferative responsesLive virus infectionT cell responsesMixed lymphocyte responseSecondary immune responsePoliovirus immunizationLymphocyte responsesVirus infectionProliferative responsePoliovirus infectionAntigenPotential mechanismsAmplification pathwayConsistent changesImmunizationInfectionPoliovirusSubjectsResponse
1984
Autoimmunity following viral infection: demonstration of monoclonal antibodies against normal tissue following infection of mice with reovirus and demonstration of shared antigenicity between virus and lymphocytes
Tardieu M, Powers M, Hafler D, Hauser S, Weiner H. Autoimmunity following viral infection: demonstration of monoclonal antibodies against normal tissue following infection of mice with reovirus and demonstration of shared antigenicity between virus and lymphocytes. European Journal Of Immunology 1984, 14: 561-565. PMID: 6329771, DOI: 10.1002/eji.1830140614.Peer-Reviewed Original ResearchConceptsNormal tissuesMonoclonal antibodiesViral infectionOnly virusInfection of miceUninfected control animalsAdult C57BL/6 miceAutoreactive monoclonal antibodiesNS1 myeloma cellsReovirus type 3Reovirus type 1Autoimmune responseC57BL/6 miceLung tissueT lymphocytesImmune responseSplenic lymphocytesControl animalsEpendymal cellsViral determinantsMyeloma cellsType 1LymphocytesInfectionReovirus type