grant
Macrophage senescence as a driver of granuloma failure and progression to necrosis in TB and TB/HIV
Organization JOHNS HOPKINS UNIVERSITYLocation BALTIMORE, UNITED STATESPosted 19 Sept 2025Deadline 31 Aug 2029
NIHUS FederalResearch GrantFY2025AIDS VirusATF-3ATF3Acquired Immune Deficiency Syndrome VirusAcquired Immunodeficiency Syndrome VirusAdoptedAgingAllelesAllelomorphsAnimal ModelAnimal Models and Related StudiesAntitubercular DrugsB7-H1BeliefBody TissuesCD274COVID-19CV-19Cell AgingCell BodyCell Communication and SignalingCell SenescenceCell Senescence InductionCell SignalingCellsCellular AgingCellular SenescenceCessation of lifeChronicClinicalCoronavirus Infectious Disease 2019CoughingDasatinibDataDeathDevelopmentDomestic RabbitDrug InteractionsDrugsDysfunctionElementsEvaluationFailureFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryFunctional disorderGranulomaGranulomatous LesionHCVHIVHIV/MtbHIV/TBHIV/mycobacterium tuberculosisHIV/tuberculosisHepatitis C virusHumanHuman Immunodeficiency VirusesHyperactivityIFNIL-1raIL1 febrile inhibitorIL1RNImmuneImmune responseImmunesImmunosuppressionImmunosuppression EffectImmunosuppressive EffectInfectionInflammatoryInterferonsInterleukin-1 Receptor AntagonistIntracellular Communication and SignalingKnowledgeLAV-HTLV-IIILesionLipid PeroxidationLungLung ParenchymaLung Respiratory SystemLung TBLung TissueLung TuberculosisLymphadenopathy-Associated VirusM tbM tuberculosisM tuberculosis infectionM. tbM. tb infectionM. tuberculosisM. tuberculosis infectionM. tuberculosis/HIVM.tb infectionM.tuberculosis infectionMTB infectionMacrophageMacrophage ActivationMediatingMedicationMiceMice MammalsModelingModern ManMolecularMurineMusMycobacterium tuberculosisMycobacterium tuberculosis (MTB) infectionMycobacterium tuberculosis infectionMyeloid CellsMφNecrosisNecroticOryctolagus cuniculusOxidative StressPD-L1PDL-1PathogenesisPathologicPathway interactionsPharmaceutical PreparationsPhenotypePhysiopathologyPlayPopulationPredispositionProgrammed Cell Death 1 Ligand 1Programmed Death Ligand 1Pulmonary TBPulmonary TuberculosisQuercetinRabbitsRabbits MammalsRegimenReplicative SenescenceResistanceRoleSIVSamplingSignal TransductionSignal Transduction SystemsSignalingSignaling MoleculeSimian Immunodeficiency VirusesStressStructure of parenchyma of lungSusceptibilityT-Cell ActivationTB drugsTB infectionTB therapyTB treatmentTestingTherapeuticTimeTissuesTuberculosisUpregulationVirus-HIVactivate T cellsactivating transcription factor 3agedanakinraanti-TB drugsanti-tuberculosis drugsbiological adaptation to stressbiological signal transductioncellular aging inductioncellular senescence inductionchallenge in rhesus macaquesco-infectioncoinfectioncombatcomparativecoronavirus disease 2019coronavirus disease-19coronavirus infectious disease-19designdesigningdevelopmentaldisseminated TBdisseminated tuberculosisdrug/agentfisetinflow cytophotometryhost responseimmune suppressionimmune suppressive activityimmune suppressive functionimmune suppressive macrophagesimmune system responseimmunoresponseimmunosuppressive activityimmunosuppressive functionimmunosuppressive macrophagesimmunosuppressive responseimprovedinfected rhesus macaquesinfected rhesus monkeyinfection due to Mycobacterium tuberculosisinfection in rhesus macaquesinfection of rhesus macaquesinterleukin 1 receptor antagonist proteinlung lesionmacromoleculemodel of animalmouse modelmtbmurine modelnon-human primatenonhuman primatenovelpathogenpathophysiologypathwaypharmacologicprogrammed cell death ligand 1programmed cell death protein ligand 1protein death-ligand 1protein homeostasisproteostasisproteotoxicproteotoxicitypulmonary lesionreaction; crisisrecruitreplicative agingresistantresponserhesus challengerhesus macaque challengerhesus monkey infectionscRNA sequencingscRNA-seqsenescencesenescence and its associated secretory phenotypesenescence associated secretomesenescence associated secretory factorssenescence associated secretory pathwaysenescence associated secretory phenotypesenescence associated secretory programsenescence associated secretory proteinssenescence inductionsenescentsenescent associated secretomesenescent associated secretory phenotypesenescent cellsenolyticssingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsmall moleculesocial rolespatial RNA sequencingspatial gene expression analysisspatial gene expression profilingspatial resolved transcriptome sequencingspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatially resolved transcriptomicsspatio transcriptomicsstress responsestress; reactiontooltranscriptomicstreat M. tuberculosistreat Mtbtreat Mycobacterium tuberculosistreat tbtreat tuberculosistuberculosis drugstuberculosis infectiontuberculosis therapytuberculosis treatmenttuberculous spondyloarthropathyurine IL-1 inhibitorurine interleukin 1 inhibitorurine-derived IL1 inhibitor
Description preview
ABSTRACT
Understanding the fundamental mechanisms of granuloma breakdown and necrosis in
pulmonary TB lesions is a key unmet need. Lung granulomatous lesions from human
active TB lung lesions show prominent markers of cellular senescence in myeloid
cells, but this aspect of granuloma breakdown has not been well-studied. In the B6.Sst1S mouse…
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