A Distinct Peripheral Blood Monocyte Phenotype Is Associated with Parasite Inhibitory Activity in Acute Uncomplicated Plasmodium falciparum Malaria

Pattamawan Chimma,Christian Roussilhon,Panudda Sratongno,Pierre Druilhe,David J. Roberts,Ronnatrai Ruangveerayuth,Kovit Pattanapanyasat,Jean-Louis Pérignon,James W. Kazura

doi:10.1371/journal.ppat.1000631

Abstract

Monocyte (MO) subpopulations display distinct phenotypes and functions which can drastically change during inflammatory states. We hypothesized that discrete MO subpopulations are induced during malaria infection and associated with anti-parasitic activity. We characterized the phenotype of blood MO from healthy malaria-exposed individuals and that of patients with acute uncomplicated malaria by flow cytometry. In addition, MO defense function was evaluated by an in vitro antibody dependent cellular inhibition (ADCI) assay. At the time of admission, the percentages and absolute numbers of CD16+ MO, and CCR2+CX3CR1+ MO, were high in a majority of patients. Remarkably, expression of CCR2 and CX3CR1 on the CD14high (hi) MO subset defined two subgroups of patients that also differed significantly in their functional ability to limit the parasite growth, through the ADCI mechanism. In the group of patients with the highest percentages and absolute numbers of CD14hiCCR2+CX3CR1+ MO and the highest mean levels of ADCI activity, blood parasitemias were lower (0.14±0.34%) than in the second group (1.30±3.34%; p = 0.0053). Data showed that, during a malaria attack, some patients' MO can exert a strong ADCI activity. These results bring new insight into the complex relationships between the phenotype and the functional activity of blood MO from patients and healthy malaria-exposed individuals and suggest discrete MO subpopulations are induced during malaria infection and are associated with anti-parasitic activity.

Highlights

Innate defenses against malaria play a vital role in the clearance of Plasmodium-infected red blood cells in murine and human infections [1,2,3,4,5]
Blood monocytes (MO) belong to the first line of defense against infectious pathogens, but little is known of MO phenotype and function during acute malaria infection
The percentage and absolute number of MO with this unusual phenotype was high in patients with low level of blood parasitemia, suggesting that activation of this particular subset of blood MO was potentially associated with the control of parasite infection

Summary

Introduction

Innate defenses against malaria play a vital role in the clearance of Plasmodium-infected red blood cells (iRBCs) in murine and human infections [1,2,3,4,5]. This innate response against iRBCs is, at least in part, related to the functional activity of monocytes (MO) macrophages and/or polymorphonuclear leukocytes. These myeloid cells can modulate the inflammatory process and trigger the adaptive immune responses. The existence of distinct MO populations in human blood was initially described by Ziegler-

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