The [CD14.sup.+][CD16.sup.+] inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria

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.sup.+][CD16.sup.-] (classical), [CD14.sup.+][CD16.sup.+] (inflammatory), and [CD14.sup.lo][CD16.sup.+] (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the [CD16.sup.+] cells, in particular the [CD14.sup.+][CD16.sup.+] monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, [CD14.sup.+] were distinguished from [CD14.sup.lo] monocytes by displaying larger and more active mitochondria. [CD14.sup.+][CD16.sup.+] monocytes were more efficient in phagocytizing P. vivaxinfected 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.sup.+][CD16.sup.+] cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection.