The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis
Inês Mesquita, Carolina Ferreira, Diana Moreira, George Eduardo Gabriel Kluck, Ana Margarida Barbosa, Egídio Torrado, Ricardo Jorge Dinis‐Oliveira, Luís G. Gonçalves, Charles-Joly Beauparlant, Arnaud Droit, Luciana Berod, Tim Sparwasser, Neelam Bodhale, Bhaskar Saha, Fernando Rodrigues, Cristina Cunha, Agostinho Carvalho, António G. Castro, Jérôme Estaquier, Ricardo Silvestre
Abstract
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.