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 ResearchTuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces
Strine MS, Wilen CB. Tuft cells are key mediators of interkingdom interactions at mucosal barrier surfaces. PLOS Pathogens 2022, 18: e1010318. PMID: 35271673, PMCID: PMC8912186, DOI: 10.1371/journal.ppat.1010318.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInterkingdom interactionsTuft cellsCell biologyImmune responseMicrobial activationMicrobial sensingCell abundanceMucosal barrier surfacesAntiviral adaptive immune responsesType 2 immune responsesCell heterogeneityExquisite specificityMucosal barrier integrityAdaptive immune responsesMurine norovirusHuman healthKey orchestratorsMicrobial infectionsPathogenic bacteriaBroad intraFlavivirus replicationKey mediatorContext of coinfectionTissue repairImmune evasion
2021
CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus
Graziano VR, Alfajaro MM, Schmitz CO, Filler RB, Strine MS, Wei J, Hsieh LL, Baldridge MT, Nice TJ, Lee S, Orchard RC, Wilen CB. CD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine Norovirus. Journal Of Virology 2021, 95: 10.1128/jvi.01652-20. PMID: 33177207, PMCID: PMC7925115, DOI: 10.1128/jvi.01652-20.Peer-Reviewed Original ResearchConceptsConditional knockout miceIntestinal epithelial cellsCell tropismKnockout miceTuft cellsDendritic cellsMyelomonocytic cellsB cellsCellular tropismMurine norovirusEpithelial cellsViral RNA levelsInnate immune responseCause of gastroenteritisMNoV infectionCell typesViral loadGastrointestinal infectionsReceptor expressionImmunocompetent humansImmune responseCell type-specific rolesMouse modelIntestinal tissueMNoV
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