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Plasmodium vivax Infection Alters Mitochondrial Metabolism in Human Monocytes

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Autor(es):
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Diniz, Suelen Queiroz [1, 2] ; Teixeira-Carvalho, Andrea [1] ; Figueiredo, Maria Marta [1] ; Carvalho Costa, Pedro Augusto [1] ; Rocha, Bruno Coelho [1] ; Martins-Filho, Olindo Assis [1] ; Goncalves, A. Ricardo [3] ; Pereira, Dhelio Batista [4] ; Tada, Mauro Shugiro [4] ; Oliveira, Fabiano [5] ; Gazzinelli, Ricardo Tostes [1, 2] ; do Valle Antonelli, Lis Ribeiro [1, 2]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Fundacao Oswaldo Cruz, Inst Rene Rachou, Belo Horizonte, MG - Brazil
[2] Univ Fed Minas Gerais, Dept Bioquim & Imunol, Inst Ciencias Biol, Belo Horizonte, MG - Brazil
[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Patol Gera, Belo Horizonte, MG - Brazil
[4] Ctr Pesquisas Med Trop Rondonia, Porto Velho, Rondonia - Brazil
[5] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD - USA
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: MBIO; v. 12, n. 4 JUL-AUG 2021.
Citações Web of Science: 0
Resumo

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. (AU)

Processo FAPESP: 16/23618-8 - Mecanismos imunológicos de resistência e patogênese da malária
Beneficiário:João Santana da Silva
Modalidade de apoio: Auxílio à Pesquisa - Temático