2024
Intestinal tuft cell immune privilege enables norovirus persistence
Strine M, Fagerberg E, Darcy P, Barrón G, Filler R, Alfajaro M, D'Angelo-Gavrish N, Wang F, Graziano V, Menasché B, Damo M, Wang Y, Howitt M, Lee S, Joshi N, Mucida D, Wilen C. Intestinal tuft cell immune privilege enables norovirus persistence. Science Immunology 2024, 9: eadi7038. PMID: 38517952, PMCID: PMC11555782, DOI: 10.1126/sciimmunol.adi7038.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsIntestinal tuft cellsT cellsTufted cellsViral persistenceSite of viral persistenceChemosensory epithelial cellsNormal antigen presentationImmune-privileged nicheIntestinal stem cellsMemory phenotypeImmune privilegeImmune escapeReporter miceAntigen presentationChronic infectionCytotoxic capacityEpithelial cellsNorovirus infectionStem cellsCell interactionsInfectionCell survivalEnteric microbesCells
2023
IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus
Ingle H, Makimaa H, Aggarwal S, Deng H, Foster L, Li Y, Kennedy E, Peterson S, Wilen C, Lee S, Suthar M, Baldridge M. IFN-λ derived from nonsusceptible enterocytes acts on tuft cells to limit persistent norovirus. Science Advances 2023, 9: eadi2562. PMID: 37703370, PMCID: PMC10499323, DOI: 10.1126/sciadv.adi2562.Peer-Reviewed Original ResearchConceptsIntestinal epithelial cellsTuft cellsUninfected bystander cellsIFN-λ signalingSource of IFNImmune cellsIntestinal infectionsLeading causeViral gastroenteritisMNoVNorovirus pathogenesisCellular tropismPotent antiviralEpidemic viral gastroenteritisEpithelial cellsBystander cellsIFNNorovirusAntiviralsInfectionMurine norovirusIntercellular communicationPersistent strainsCellsVivo
2022
Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity
Strine M, Alfajaro M, Graziano V, Song J, Hsieh L, Hill R, Guo J, VanDussen K, Orchard R, Baldridge M, Lee S, Wilen C. Tuft-cell-intrinsic and -extrinsic mediators of norovirus tropism regulate viral immunity. Cell Reports 2022, 41: 111593. PMID: 36351394, PMCID: PMC9662704, DOI: 10.1016/j.celrep.2022.111593.Peer-Reviewed Original Research
2020
Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity
Brestoff JR, Wilen CB, Moley JR, Li Y, Zou W, Malvin NP, Rowen MN, Saunders BT, Ma H, Mack MR, Hykes BL, Balce DR, Orvedahl A, Williams JW, Rohatgi N, Wang X, McAllaster MR, Handley SA, Kim BS, Doench JG, Zinselmeyer BH, Diamond MS, Virgin HW, Gelman AE, Teitelbaum SL. Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity. Cell Metabolism 2020, 33: 270-282.e8. PMID: 33278339, PMCID: PMC7858234, DOI: 10.1016/j.cmet.2020.11.008.Peer-Reviewed Original ResearchConceptsIntercellular mitochondria transferMitochondria transferMitochondria uptakeMetabolic homeostasisGenome-wide CRISPRWhite adipose tissue homeostasisWAT macrophagesDistinct macrophage subpopulationsKnockout screensTissue homeostasisHeparan sulfateAdipose tissue homeostasisWhite adipose tissueGenes EXT1HomeostasisImmunometabolic crosstalkMitochondriaAdipocytesMyeloid cellsMacrophage subpopulationsCellsVivoRecent studiesMacrophagesCRISPR
2019
A Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis
Lee S, Liu H, Wilen CB, Sychev ZE, Desai C, Hykes BL, Orchard RC, McCune BT, Kim KW, Nice TJ, Handley SA, Baldridge MT, Amarasinghe GK, Virgin HW. A Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis. Cell Host & Microbe 2019, 25: 845-857.e5. PMID: 31130511, PMCID: PMC6622463, DOI: 10.1016/j.chom.2019.04.005.Peer-Reviewed Original ResearchConceptsNS1 secretionTuft cellsIFN-λ responseAnti-capsid antibodiesMNoV infectionAcute infectionIntestinal infectionsLack of inductionPersistent infectionNorovirus pathogenesisCaspase-3 cleavageIFN responseInfectionSecretionViral nonstructural proteinsIFNProtein 1/2Viral proteinsMurine norovirusNS1Lower percentageNonstructural proteinsCellsLow numberVaccination
2018
Tropism for tuft cells determines immune promotion of norovirus pathogenesis
Wilen CB, Lee S, Hsieh LL, Orchard RC, Desai C, Hykes BL, McAllaster MR, Balce DR, Feehley T, Brestoff JR, Hickey CA, Yokoyama CC, Wang YT, MacDuff DA, Kreamalmayer D, Howitt MR, Neil JA, Cadwell K, Allen PM, Handley SA, van Lookeren Campagne M, Baldridge MT, Virgin HW. Tropism for tuft cells determines immune promotion of norovirus pathogenesis. Science 2018, 360: 204-208. PMID: 29650672, PMCID: PMC6039974, DOI: 10.1126/science.aar3799.Peer-Reviewed Original ResearchConceptsVirus infectionImmune promotionTuft cellsType 2 cytokinesEnteric virus infectionEnteric viral infectionsIntestinal epithelial cellsMNoV infectionNorovirus infectionCommensal microbiotaHost immunityViral infectionNorovirus pathogenesisRare typeImmune systemCellular tropismInfectionMouse intestineTarget cellsEpithelial cellsCell proliferationCytokinesTropismCD300lfCells
2016
Discovery of a proteinaceous cellular receptor for a norovirus
Orchard RC, Wilen CB, Doench JG, Baldridge MT, McCune BT, Lee YC, Lee S, Pruett-Miller SM, Nelson CA, Fremont DH, Virgin HW. Discovery of a proteinaceous cellular receptor for a norovirus. Science 2016, 353: 933-936. PMID: 27540007, PMCID: PMC5484048, DOI: 10.1126/science.aaf1220.Peer-Reviewed Original ResearchConceptsProteinaceous receptorsMNoV infectionCellular machineryNoV replicationHuman cellsCell deathSpecies barrierCD300lfSpecies tropismPrimary cellsCellular receptorsCell linesMurine NoVHost factorsReplicationCause of gastroenteritisPrimary determinantNoV infectionReceptorsCellsEctodomainMachineryInfectionCrystal structureResidues
2013
Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection
Didigu CA, Wilen CB, Wang J, Duong J, Secreto AJ, Danet-Desnoyers GA, Riley JL, Gregory PD, June CH, Holmes MC, Doms RW. Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection. Blood 2013, 123: 61-69. PMID: 24162716, PMCID: PMC3879906, DOI: 10.1182/blood-2013-08-521229.Peer-Reviewed Original ResearchConceptsC chemokine receptor 5HIV-1 infectionT cellsHIV-1HIV coreceptor CCR5Chemokine receptor 5Humanized mouse modelDrug-free treatmentHIV-1 entryHIV coreceptorsPharmacologic blockadeCoreceptor CCR5Mouse modelCells engraftReceptor 5Gene-modified cellsCXCR4InfectionPrimary humanCoreceptorCD4CCR5Genetic inactivationVirusCells