2024
Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virus
2021
RIPK3 Activates MLKL-mediated Necroptosis and Inflammasome Signaling during Streptococcus Infection.
Huang HR, Cho SJ, Harris RM, Yang J, Bermejo S, Sharma L, Dela Cruz CS, Xu JF, Stout-Delgado HW. RIPK3 Activates MLKL-mediated Necroptosis and Inflammasome Signaling during Streptococcus Infection. American Journal Of Respiratory Cell And Molecular Biology 2021, 64: 579-591. PMID: 33625952, PMCID: PMC8086037, DOI: 10.1165/rcmb.2020-0312oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsCalcium ChannelsCase-Control StudiesDisease Models, AnimalFemaleGene Expression RegulationHumansInflammasomesMacrophages, AlveolarMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMitochondriaMitochondrial Permeability Transition PoreNecroptosisNLR Family, Pyrin Domain-Containing 3 ProteinPneumonia, PneumococcalProtein KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesReceptor-Interacting Protein Serine-Threonine KinasesSignal TransductionStreptococcus pneumoniaeConceptsCommunity-acquired pneumoniaPneumococcal pneumoniaSevere pathological damageHealthy control subjectsPotential plasma markerNLRP3 inflammasome activationCommon bacterial pathogensMitochondrial permeability transition pore openingStreptococcal pneumoniaPlasma markersStreptococcus infectionBacterial clearanceControl subjectsPathological damageLeading causeMitochondrial reactive oxygenInflammasome activationMurine modelMitochondrial calcium uptakePneumoniaPermeability transition pore openingHuman studiesHigh mortalityInflammasome signalingTransition pore openingCutting Edge: Severe SARS-CoV-2 Infection in Humans Is Defined by a Shift in the Serum Lipidome, Resulting in Dysregulation of Eicosanoid Immune Mediators
Schwarz B, Sharma L, Roberts L, Peng X, Bermejo S, Leighton I, Casanovas-Massana A, Minasyan M, Farhadian S, Ko AI, Team Y, Dela Cruz CS, Bosio CM. Cutting Edge: Severe SARS-CoV-2 Infection in Humans Is Defined by a Shift in the Serum Lipidome, Resulting in Dysregulation of Eicosanoid Immune Mediators. The Journal Of Immunology 2021, 206: ji2001025. PMID: 33277388, PMCID: PMC7962598, DOI: 10.4049/jimmunol.2001025.Peer-Reviewed Original ResearchConceptsLipid mediatorsRisk factorsSevere diseaseSevere SARS-CoV-2 infectionHospitalized COVID-19 patientsSARS-CoV-2 infectionImportant immune regulatory roleSevere COVID-19COVID-19 patientsImmune regulatory roleProinflammatory lipid mediatorsCOVID-19Immunomodulatory eicosanoidsImmune mediatorsSerum lipidomeAdvanced agePatientsCOVID-19 pandemicCytochrome P450MortalityDiseaseDysregulationMediatorsLMS productsLipidome
2020
The kinetics of humoral response and its relationship with the disease severity in COVID-19
Ren L, Zhang L, Chang D, Wang J, Hu Y, Chen H, Guo L, Wu C, Wang C, Wang Y, Wang Y, Wang G, Yang S, Dela Cruz CS, Sharma L, Wang L, Zhang D, Wang J. The kinetics of humoral response and its relationship with the disease severity in COVID-19. Communications Biology 2020, 3: 780. PMID: 33311543, PMCID: PMC7733479, DOI: 10.1038/s42003-020-01526-8.Peer-Reviewed Original ResearchConceptsHumoral responseDisease severityReceptor-binding domainAntibody titersSpike proteinSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2COVID-19Respiratory syndrome coronavirus 2Titers of NAbsGeometric mean titersCOVID-19 patientsSyndrome coronavirus 2Coronavirus disease 2019Disease courseMean titersCoronavirus 2Antibody responseIgG antibodiesRisk factorsIg levelsImmunoglobulin ADisease 2019Severe casesModerate infectionsSevere respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia
Gautam S, Cohen AJ, Stahl Y, Toro P, Young GM, Datta R, Yan X, Ristic NT, Bermejo SD, Sharma L, Restrepo M, Dela Cruz CS. Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia. Thorax 2020, 75: 974-981. PMID: 32826284, DOI: 10.1136/thoraxjnl-2020-214896.Peer-Reviewed Original ResearchConceptsPure viral infectionBacterial coinfectionViral infectionInfluenza infectionSevere respiratory viral infectionsAbility of procalcitoninRetrospective cohort studyViral respiratory infectionsRespiratory viral infectionsMarker of severityRespiratory viral illnessSevere viral infectionsSpecificity of procalcitoninCharacteristic curve analysisCellular modelHigher procalcitoninProcalcitonin expressionElevated procalcitoninCohort studyViral illnessRespiratory infectionsAntibiotic administrationBacterial pneumoniaSevere diseaseProcalcitoninPersistent Viral Presence Determines the Clinical Course of the Disease in COVID-19
Chang D, Zhao P, Zhang D, Dong JH, Xu Z, Yang G, Li BY, Liu HX, Li BA, Qin CF, Peng XH, Wang FS, Xie LX, Chen Z, Dela Cruz CS, Sharma L, Qin EQ. Persistent Viral Presence Determines the Clinical Course of the Disease in COVID-19. The Journal Of Allergy And Clinical Immunology In Practice 2020, 8: 2585-2591.e1. PMID: 32574840, PMCID: PMC7305869, DOI: 10.1016/j.jaip.2020.06.015.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBetacoronavirusC-Reactive ProteinChildChild, PreschoolComorbidityCoronavirus InfectionsCOVID-19FemaleGlucocorticoidsHumansInfantInflammationInflammation MediatorsInterleukin-6MaleMiddle AgedPandemicsPneumonia, ViralReal-Time Polymerase Chain ReactionRespiration, ArtificialSARS-CoV-2Severity of Illness IndexYoung AdultConceptsDisease severityViral clearanceViral persistenceDisease outcomeCOVID-19Viral presenceExtensive lung involvementC-reactive proteinEffective antiviral therapyCoronavirus disease 2019Severe disease outcomesHost antiviral mechanismsInfectious viral particlesImmunomodulatory therapyInflammatory markersLung involvementRespiratory supportClinical courseAntiviral therapyIL-6Viral reactivationClinical managementInflammatory responseChest imagingDisease 2019Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection
Chang D, Mo G, Yuan X, Tao Y, Peng X, Wang FS, Xie L, Sharma L, Dela Cruz CS, Qin E. Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection. American Journal Of Respiratory And Critical Care Medicine 2020, 201: 1150-1152. PMID: 32200654, PMCID: PMC7193851, DOI: 10.1164/rccm.202003-0524le.Peer-Reviewed Original ResearchProfiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)
Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, Dela Cruz CS, Wang Y, Wu C, Xiao Y, Zhang L, Han L, Dang S, Xu Y, Yang Q, Xu S, Zhu H, Xu Y, Jin Q, Sharma L, Wang L, Wang J. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clinical Infectious Diseases 2020, 71: 778-785. PMID: 32198501, PMCID: PMC7184472, DOI: 10.1093/cid/ciaa310.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Humoral responseSymptom onsetIgM ELISAProbable casesEarly humoral responseHost humoral responseMajor healthcare threatCoronavirus disease 2019IgA antibody detectionCOVID-19Viral nucleic acidsQuantitative polymerase chain reactionNovel coronavirus diseaseFalse-negative resultsMedian durationAntibody testingIgG responsesIgM antibodiesInfected patientsPolymerase chain reactionPositive rateDisease 2019Healthcare threatSubclinical casesEpidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China
Chang D, Lin M, Wei L, Xie L, Zhu G, Dela Cruz CS, Sharma L. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA 2020, 323: 1092-1093. PMID: 32031568, PMCID: PMC7042871, DOI: 10.1001/jama.2020.1623.Peer-Reviewed Original Research
2019
Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity
Solis AG, Bielecki P, Steach HR, Sharma L, Harman CCD, Yun S, de Zoete MR, Warnock JN, To SDF, York AG, Mack M, Schwartz MA, Dela Cruz CS, Palm NW, Jackson R, Flavell RA. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature 2019, 573: 69-74. PMID: 31435009, PMCID: PMC6939392, DOI: 10.1038/s41586-019-1485-8.Peer-Reviewed Original ResearchConceptsInnate immune cellsImmune cellsInflammatory responseInnate immune systemCyclical hydrostatic pressurePulmonary inflammationImmune responseImmune systemInnate immunityBacterial infectionsIon channel Piezo1InflammationPhysiological fluctuationsImmunityPhysiological roleLocal microenvironmentCellsPiezo1Direct recognitionResponseAutoinflammationLungInfectionMice
2018
The fungal ligand chitin directly binds TLR2 and triggers inflammation dependent on oligomer size
Fuchs K, Cardona Gloria Y, Wolz O, Herster F, Sharma L, Dillen CA, Täumer C, Dickhöfer S, Bittner Z, Dang T, Singh A, Haischer D, Schlöffel MA, Koymans KJ, Sanmuganantham T, Krach M, Roger T, Le Roy D, Schilling NA, Frauhammer F, Miller LS, Nürnberger T, LeibundGut‐Landmann S, Gust AA, Macek B, Frank M, Gouttefangeas C, Dela Cruz CS, Hartl D, Weber AN. The fungal ligand chitin directly binds TLR2 and triggers inflammation dependent on oligomer size. EMBO Reports 2018, 19: embr201846065. PMID: 30337494, PMCID: PMC6280652, DOI: 10.15252/embr.201846065.Peer-Reviewed Original ResearchConceptsTLR2 ligandsInnate immune receptors Toll-like receptorToll-like receptorsMurine immune cellsImmune activationDistinct signaling outcomesImmune cellsNovel therapiesTriggers inflammationImmuno-modulationFungal infectionsInflammationImmune receptorsPotential targetTLR2Unknown purityReceptorsNanomolar affinityAsthmaHumansTherapyInfectionFungal diseasesDiseasePathology
2017
The microbiome of the lung and its extracellular vesicles in nonsmokers, healthy smokers and COPD patients
Kim HJ, Kim YS, Kim KH, Choi JP, Kim YK, Yun S, Sharma L, Dela Cruz CS, Lee JS, Oh YM, Lee SD, Lee SW. The microbiome of the lung and its extracellular vesicles in nonsmokers, healthy smokers and COPD patients. Experimental & Molecular Medicine 2017, 49: e316-e316. PMID: 28408748, PMCID: PMC5420800, DOI: 10.1038/emm.2017.7.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseCOPD groupLung tissueClinical characteristicsHealthy smokersNormal spirometryPresence of COPDExtracellular vesiclesHealthy smoker groupParticipants' clinical characteristicsSurgical lung tissueObstructive pulmonary diseaseChronic inflammatory diseaseSame mean ageRibosomal RNA gene sequencingRNA gene sequencingCOPD patientsSmoker groupImmune dysfunctionPulmonary diseaseSmoking statusMean ageNanometer-sized extracellular vesiclesLung microbiomeInflammatory diseases