Enhanced Glycolysis Is Required for Antileishmanial Functions of Neutrophils Upon Infection With Leishmania donovani

• DOI: 10.3389/fimmu.2021.632512
• Publication Date: 2021-03-19T04:48:11Z
• Authors: Mareike Ohms; Carolina Ferreira; Hauke Busch; Inken Wohlers; Ana Cristina Guer...; Ricardo Silvestre; Tamás Laskay
• Keywords: Neutrophil Extracellular Traps

Visceral leishmaniasis (VL) is a fatal parasitic disease if untreated. Treatment options of VL diminish due to emerging drug resistance. Although the principal host cells for multiplication Leishmania are macrophages, neutrophils first infected with parasites rapidly after parasite inoculation. can survive in despite potent antimicrobial effector functions that eliminate parasites. Recently, growing field immunometabolism provided strong evidence therapeutic potential targeting metabolic processes as means controlling immune functions. Therefore, understanding immunometabolic profile during infection could provide new promising targets host-directed therapies against VL. To our knowledge, this study addressing bioenergetics L. donovani-infected primary human neutrophils. Transcriptome analysis revealed an early significant upregulation several glycolytic enzymes. Extracellular flux showed glycolysis and capacity were upregulated at 6 h post infection. An increased glucose uptake accumulation end products further signs elevated metabolism At same time point, oxidative phosphorylation NADPH burst but did not contribute ATP production. Inhibition 2-DG significantly reduced survival donovani promastigotes culture. However, reduction was direct antileishmanial effect consequence enhanced activity address impact days vivo, we treated C57BL/6 mice prior assessed load one day seven Our results show, post-infection animals higher than mock animals. This data indicates serves major energy source donovani. abrogates important neutrophil necessary initial control