title: The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.
abstract: Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax-infected patients display significant increase in circulating monocytes, which were defined as CD14(+)CD16- (classical), CD14(+)CD16(+) (inflammatory), and CD14loCD16(+) (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16(+) cells, in particular the CD14(+)CD16(+) monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14(+) were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14(+)CD16(+) monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14(+)CD16(+) cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection.
authors.affiliation: Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lis R V
authors.initials: LR
authors.lastname: Antonelli
authors.affiliation: Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fabiana M S
authors.initials: FM
authors.lastname: Leoratti
authors.affiliation: Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Pedro A C
authors.initials: PA
authors.lastname: Costa
authors.affiliation: Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil; Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Rocha
authors.affiliation: Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Suelen Q
authors.initials: SQ
authors.lastname: Diniz
authors.affiliation: Centro de Pesquisas em Medicina Tropical de Rondônia, Porto Velho, Rondônia, Brazil.
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Tada
authors.affiliation: Centro de Pesquisas em Medicina Tropical de Rondônia, Porto Velho, Rondônia, Brazil.
authors.forename: Dhelio B
authors.initials: DB
authors.lastname: Pereira
authors.affiliation: Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.affiliation: Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gonçalves
authors.affiliation: Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil; Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D010587:Phagocytosis; D010966:Plasmodium vivax / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology*; D055815:Young Adult
chemical_list: D018950:Lipopolysaccharide Receptors; D017382:Reactive Oxygen Species; D017452:Receptors, IgG