A distinct peripheral blood monocyte phenotype is associated with parasite inhibitory activity in acute uncomplicated Plasmodium falciparum malaria.
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 CD14(high (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 CD14(hi)CCR2+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.
Bio-medical Parasitology Unit, Institut Pasteur, Paris, France.
Pattamawan
P
Chimma
Christian
C
Roussilhon
Panudda
P
Sratongno
Ronnatrai
R
Ruangveerayuth
Kovit
K
Pattanapanyasat
Jean-Louis
JL
Pérignon
David J
DJ
Roberts
Pierre
P
Druilhe
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000469:parasitology; D007371:Interferon-gamma / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016778:Malaria, Falciparum / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000469:parasitology*; D008565:Membrane Proteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D010641:Phenotype; D010963:Plasmodium falciparum / Q000276:immunology*; D054390:Receptors, CCR2 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
C515334:CCR2 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma