Twincorehttp://hdl.handle.net/10033/568762024-03-29T11:33:58Z2024-03-29T11:33:58ZThe Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis.Mesquita, InêsFerreira, CarolinaMoreira, DianaKluck, George Eduardo GabrielBarbosa, Ana MargaridaTorrado, EgídioDinis-Oliveira, Ricardo JorgeGonçalves, Luís GafeiraBeauparlant, Charles-JolyDroit, ArnaudBerod, LucianaSparwasser, TimBodhale, NeelamSaha, BhaskarRodrigues, FernandoCunha, CristinaCarvalho, AgostinhoCastro, António GilEstaquier, JérômeSilvestre, Ricardohttp://hdl.handle.net/10033/6232192022-06-14T01:56:32Z2020-03-24T00:00:00ZThe Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis.
Mesquita, Inês; Ferreira, Carolina; Moreira, Diana; Kluck, George Eduardo Gabriel; Barbosa, Ana Margarida; Torrado, Egídio; Dinis-Oliveira, Ricardo Jorge; Gonçalves, Luís Gafeira; Beauparlant, Charles-Joly; Droit, Arnaud; Berod, Luciana; Sparwasser, Tim; Bodhale, Neelam; Saha, Bhaskar; Rodrigues, Fernando; Cunha, Cristina; Carvalho, Agostinho; Castro, António Gil; Estaquier, Jérôme; Silvestre, Ricardo
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 infected HIF-1α-/- macrophages. L. donovani-infected HIF-1α-deficient mice develop hypertriglyceridemia and lipid accumulation in splenic and hepatic myeloid cells. Most importantly, our data demonstrate that manipulating FASN or SREBP-1c using pharmacological inhibitors significantly reduced parasite burden. As such, genetic deficiency of HIF-1α is associated with increased lipid accumulation, which results in impaired host-protective anti-leishmanial functions of myeloid cells.
2020-03-24T00:00:00ZCharacterization of Clostridioides difficile DSM 101085 with A-B-CDT+ Phenotype from a Late Recurrent Colonization.Riedel, ThomasNeumann-Schaal, MeinaWittmann, JohannesSchober, IsabelHofmann, Julia DanielleLu, Chia-WenDannheim, AntoniaZimmermann, OrtrudLochner, MatthiasGroß, UweOvermann, Jörghttp://hdl.handle.net/10033/6231962022-06-14T01:57:16Z2020-01-01T00:00:00ZCharacterization of Clostridioides difficile DSM 101085 with A-B-CDT+ Phenotype from a Late Recurrent Colonization.
Riedel, Thomas; Neumann-Schaal, Meina; Wittmann, Johannes; Schober, Isabel; Hofmann, Julia Danielle; Lu, Chia-Wen; Dannheim, Antonia; Zimmermann, Ortrud; Lochner, Matthias; Groß, Uwe; Overmann, Jörg
2020-01-01T00:00:00ZHepatocyte transplantation, a step forward?Ott, MichaelCastell, Jose Vhttp://hdl.handle.net/10033/6218402019-08-30T11:26:09Z2019-06-01T00:00:00ZHepatocyte transplantation, a step forward?
Ott, Michael; Castell, Jose V
Editorial
2019-06-01T00:00:00ZC-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function.Wang, YongDembowsky, KlausChevalier, EricStüve, PhilippKorf-Klingebiel, MortimerLochner, MatthiasNapp, L ChristianFrank, HeikeBrinkmann, EvaKanwischer, AnnaBauersachs, JohannGyongyosi, MariannSparwasser, TimWollert, Kai Chttp://hdl.handle.net/10033/6216822019-08-30T11:32:39Z2019-01-30T00:00:00ZC-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-Regulatory Function.
Wang, Yong; Dembowsky, Klaus; Chevalier, Eric; Stüve, Philipp; Korf-Klingebiel, Mortimer; Lochner, Matthias; Napp, L Christian; Frank, Heike; Brinkmann, Eva; Kanwischer, Anna; Bauersachs, Johann; Gyongyosi, Mariann; Sparwasser, Tim; Wollert, Kai C
Acute myocardial infarction (MI) elicits an inflammatory response that drives tissue repair and adverse cardiac remodeling. Inflammatory cell trafficking after MI is controlled by C X-C motif chemokine ligand 12 (CXCL12) and its receptor, C-X-C motif chemokine receptor 4 (CXCR4). CXCR4 antagonists mobilize inflammatory cells and promote infarct repair, but the cellular mechanisms are unclear. We investigated the therapeutic potential and mode of action of the peptidic macrocycle CXCR4 antagonist POL5551 in mice with reperfused MI. We applied cell depletion and adoptive transfer strategies using lymphocyte-deficient Rag1 knockout mice; DEREG mice, which express a diphtheria toxin receptor-enhanced green fluorescent protein fusion protein under the control of the promoter/enhancer region of the regulatory T (T Intraperitoneal POL5551 injections in wild-type mice (8 mg/kg at 2, 4, 6, and 8 d) enhanced angiogenesis in the infarct border-zone, reduced scar size, and attenuated left ventricular remodeling and contractile dysfunction at 28 d. Treatment effects were absent in splenectomized wild-type mice, Rag1 knockout mice, and T Our data confirm CXCR4 blockade as a promising treatment strategy after MI. We identify dendritic cell-primed splenic T
2019-01-30T00:00:00Z