The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

PLoS Pathogens

Andrea Teixeira-Carvalho¹  Dhelio B. Pereira¹  Suelen Q. Diniz²  Ricardo T. Gazzinelli³  Ricardo Gonçalves⁴  Douglas T. Golenbock⁵  Pedro A. C. Costa⁶  Fabiana M. S. Leoratti⁶  Lis R. V. Antonelli⁶  Bruno C. Rocha⁶  Mauro S. Tada⁶ 

[1] Centro de Pesquisas em Medicina Tropical de Rondônia, Porto Velho, Rondônia, Brazil;Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America;Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil;Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil

关键词: Monocytes;    Malaria;    Plasmodium;    Inflammation;    Mitochondria;    Phagocytosis;    Malarial parasites;    Reticulocytes;   

DOI  :  10.1371/journal.ppat.1004393

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY