0000000000084633

AUTHOR

Agostinho Carvalho

0000-0001-8935-8030

showing 2 related works from this author

The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis

2020

Summary: Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L. donovani infection through increased lipogenesis. Absence of HIF-1α leads to a defect in BNIP3 expression, resulting in the activation of mTOR and nuclear translocation of SREBP-1c. We observed the induction of lipogenic gene transcripts, such as FASN, and lipid accumulation in inf…

0301 basic medicineSREBP-1cHIF1A Gene[SDV]Life Sciences [q-bio]Leishmania donovaniHIF-1αGeneral Biochemistry Genetics and Molecular BiologyMitochondrial Proteins03 medical and health sciences0302 clinical medicinevisceral leishmaniasisAnimalsHumansMyeloid Cellslcsh:QH301-705.5GenelipogenesisPI3K/AKT/mTOR pathwayDisease ResistanceMice Inbred BALB CInnate immune systembiologyIntracellular parasiteLipogenesisMacrophagesTOR Serine-Threonine KinasesGenetic VariationMembrane Proteinsbiology.organism_classificationLeishmaniaHypoxia-Inducible Factor 1 alpha SubunitFASNLipidsmacrophages3. Good healthCell biologyUp-RegulationMice Inbred C57BL030104 developmental biologylcsh:Biology (General)myeloid cellsLipogenesisLeishmaniasis VisceralDisease SusceptibilityacetateSterol Regulatory Element Binding Protein 1030217 neurology & neurosurgeryLeishmania donovaniSignal Transduction
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Polymorphisms within the TNFSF4 and mapkapk2 loci influence the risk of developing invasive aspergillosis: A two-stage case control study in the cont…

2020

Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a twostage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungi…

Microbiology (medical)Thymic stromal lymphopoietinCiências Médicas::Ciências da Saúde:Ciências da Saúde [Ciências Médicas]lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]Context (language use)Single-nucleotide polymorphismPlant ScienceCD38BiologyMonocytes03 medical and health sciencesAll institutes and research themes of the Radboud University Medical Center0302 clinical medicineGenotypeB cells; MAPKAPK2; TNFSF14; TNFSF4; TSLP; genetic susceptibility; invasive aspergillosis; monocytes; serum biomarkersB cells; Genetic susceptibility; Invasive aspergillosis; MAPKAPK2; Monocytes; Serum biomarkers; TNFSF14; TNFSF4; TSLPGenetic predispositionGenetic susceptibilityddc:610Allelelcsh:QH301-705.5Ecology Evolution Behavior and Systematics030304 developmental biology0303 health sciencesB cellsTNFSF14Science & TechnologyTNFSF4Case-control studyMAPKAPK2Serum biomarkers<i>TNFSF4</i>3. Good healthSettore MED/15 - MALATTIE DEL SANGUE<i>MAPKAPK2</i>lcsh:Biology (General)TSLPImmunologyInvasive aspergillosis030215 immunology
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