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

Infection onocy e 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 rnonocytes 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 CD14(lo)CD16(+) (patrolling) cells. while the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytoktnes, the CD16(+) cells, in particular the CD14(+) CD16(+) monocytes, expressed the highest levels of activation markers, which included hemokine receptors and adhesion molecules. Morphologically, CD14(+) were distinguished from CD14(lo) 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-alpha 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.