High IFN-gamma and TNF production by peripheral NK cells of Colombian patients with different clinical presentation of Plasmodium falciparum

Abstract

BackgroundIn Colombia, Plasmodium falciparum infection rarely results in severe disease or mortality compared to infections in African populations. During natural infection NK cells exhibit a cytolytic effect and regulate dendritic cells, macrophages, neutrophils as well as affect antigen specific T and B cell responses. To characterize the NK cells in P. falciparum infected patients of a highly endemic region of Colombia, the degree of NK proliferation and production of IFN gamma and TNF production in these cells were explored.MethodsSeventeen patients with acute and three with severe P. falciparum malaria patients from the Northwest region of the country were recruited in the study. In addition, 20 healthy controls were included: 10 from Medellin (no-transmission area) and 10 from the Uraba region (a malaria endemic area). Immunophenotypic analysis of peripheral mononuclear cells was performed by FACS to detect total number of NK cells, subtypes and intracellular IFNγ and TNF production by NK cells in the different patient groups.ResultsThe total mean CD56+/CD3- NK cell proportions in acute and severe malaria subjects were 9.14% (7.15%CD56dim, 2.01%CD56bright) and 19.62% (16.05%CD56dim, 3.58%CD56bright), respectively, in contrast to healthy controls from endemic (total mean CD56+/CD3-1.2%) and non-endemic area (total mean CD56+/CD3- 0.67%). Analysis of basal IFNγ and TNF levels confirmed the CD56bright NK population as the main cytokine producer (p < 0.0001) in the groups affected with malaria, with the CD56dim NK cell exhibiting the highest potential of TNF production after stimulus in the acute malaria group.ConclusionsThe results confirm the important role of not only CD56bright but also of CD56dim NK cell populations as producers of the two cytokines in malaria patients in Colombia.

STING-Licensed Macrophages Prime Type I IFN Production by Plasmacytoid Dendritic Cells in the Bone Marrow during Severe Plasmodium yoelii Malaria

“…While NK cell blood proportions did not differ in acutely infected versus follow-up patients, these cells were strongly activated in severe malaria patients and in the Py mouse model, in line with prior in vitro reports [64–66]. Likewise and as also suggested before [67], a slight decrease in the blood proportion of CD8 + and CD4 + T cells was observed in severe malaria patients and both subsets of T lymphocytes underwent robust activation, proliferation and differentiation.…”

Profile of Natural Killer (NK) Cells in Simple Malaria in Adults

“…In contrast to the results of our study, NK cells appear to play an important role in the evolution of malaria [16]. Studies reveal that NK cells are among the first cells to respond to Plasmodium falciparum by producing IFN-gamma demonstrated by in vitro and in vivo studies [17]. These cells increase particularly in number [18].…”

“…These cells increase particularly in number [18]. This role of NK has also been emphasized by several authors during simple [17] and severe manifestations of malaria [16][17][18][19]. However, studies of the dynamics of NK cells activity in patients with malaria have revealed heterogeneous results, particularly in individuals infected with P. falciparum [17].…”

Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells

“…5). Studies suggest that IFN-γ is produced by NK cells in malaria patients (20) and during in vitro culture with iRBCs (13). However, the role of IFN-γ in the antimalaria response is poorly understood.…”