Journal Article

Plasmodium vivax Infection Alters Mitochondrial Metabolism in Human Monocytes

Diniz, Suelen Queiroz, Martins-Filho, Olindo Assis, Figueiredo, Maria Marta, Teixeira-Carvalho, Andréa, Rocha, Bruno Coelho, Gazzinelli, Ricardo Tostes, Pereira, Dhélio Batista, Costa, Pedro Augusto Carvalho, Antonelli, Lis Ribeiro do Valle, Gonçalves, Ricardo, Oliveira, Fabiano, Tada, Mauro Shugiro

2021

Overview

Plasmodium vivax is the most widely distributed causative agent of human malaria. To achieve parasite control, the human immune system develops a substantial inflammatory response that is also responsible for the symptoms of the disease. Monocytes play an important role in the host defense against Plasmodium vivax as the main source of inflammatory cytokines and mitochondrial reactive oxygen species (mROS). Here, we show that monocyte metabolism is altered during human P. vivax malaria, with mitochondria playing a major function in this switch. The process involves a reprograming in which the cells increase glucose uptake and produce ATP via glycolysis instead of oxidative phosphorylation. P. vivax infection results in dysregulated mitochondrial gene expression and in altered membrane potential leading to mROS increase rather than ATP production. When monocytes were incubated with P. vivax -infected reticulocytes, mitochondria colocalized with phagolysosomes containing parasites representing an important source mROS. Importantly, the mitochondrial enzyme superoxide dismutase 2 (SOD2) is simultaneously induced in monocytes from malaria patients. Taken together, the monocyte metabolic reprograming with an increased mROS production may contribute to protective responses against P. vivax while triggering immunomodulatory mechanisms to circumvent tissue damage. IMPORTANCE Plasmodium vivax is the most widely distributed causative agent of human malaria. To achieve parasite control, the human immune system develops a substantial inflammatory response that is also responsible for the symptoms of the disease. Among the cells involved in this response, monocytes play an important role. Here, we show that monocyte metabolism is altered during malaria, with its mitochondria playing a major function in this switch. This change involves a reprograming process in which the cells increase glucose uptake and produce ATP via glycolysis instead of oxidative phosphorylation. The resulting altered mitochondrial membrane potential leads to an increase in mitochondrial reactive oxygen species rather than ATP. These data suggest that agents that change metabolism should be investigated and used with caution during malaria.

• Publisher: American Society for Microbiology
• Subject: Adenosine Triphosphate - metabolism / Adolescent / Adult / Aged / Bioenergetics / Blood parasites / Female / Gene Expression / Glucose / Glycolysis / Humans / Immune response / Immune system / Immunology / Immunomodulation / Infections / Inflammation / Malaria / Malaria, Vivax - immunology / Malaria, Vivax - physiopathology / Male / Membrane potential / Metabolism / Metabolites / Middle Aged / Mitochondria / Mitochondria - genetics / Mitochondria - metabolism / Mitochondria - pathology / mitochondrial metabolism / Monocytes / Monocytes - cytology / Monocytes - immunology / Monocytes - metabolism / Monocytes - pathology / Oxidative phosphorylation / P. vivax / Parasites / Phagolysosomes / Phagosomes - immunology / Phagosomes - parasitology / Phosphorylation / Plasmodium vivax / Plasmodium vivax - genetics / Plasmodium vivax - immunology / Plasmodium vivax - pathogenicity / Reactive oxygen species / Reactive Oxygen Species - metabolism / Research Article / Respiration / Reticulocytes / Reticulocytes - parasitology / Superoxide Dismutase - genetics / Superoxide Dismutase - metabolism / Young Adult