Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/51772
Type
ArticleCopyright
Open access
Collections
Metadata
Show full item record7
CITATIONS
7
Total citations
5
Recent citations
2.06
Field Citation Ratio
0.51
Relative Citation Ratio
PLASMODIUM VIVAX INFECTION ALTERS MITOCHONDRIAL METABOLISM IN HUMAN MONOCYTES
malaria
metabolism
mitochondria
mitochondrial metabolism
monocytes
reactive oxygen species
Author
Affilliation
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Departamento de Patologia Geral. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.
Centro de Pesquisas em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.
Centro de Pesquisas em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.
National Institutes of Healthgrid. Laboratory of Malaria and Vector Research. Rockville, Maryland, USA
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Universidade Federal de Minas Gerais. Departamento de Patologia Geral. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.
Centro de Pesquisas em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.
Centro de Pesquisas em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.
National Institutes of Healthgrid. Laboratory of Malaria and Vector Research. Rockville, Maryland, USA
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Instituto de Ciências Biológicas. Belo Horizonte, MG, Brazil.
Abstract
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.
Keywords
P. vivaxmalaria
metabolism
mitochondria
mitochondrial metabolism
monocytes
reactive oxygen species
Share