Plasmodium falciparum Malaria Carriage Associates with Reduced γδ T-Cell and NK Cell Responses to Infected Red Blood Cells In Vitro

Author(s): Bourèma Kouriba, Modibo Daou, Charles Arama, Nicolas Ouédraogo, Karamoko Niaré, Yamoussa Keita, Sibiri Sissoko, Boucary Ouologuem, Seydou Arama, Ogobara K Doumbo, Robert W Sauerwein, Anja Scholzen

Background: Innate immune cells including γδ T-cells and NK cells are directly activated by Plasmodium falciparum parasites and contribute to the control of parasitaemia. The aim of this study was to determine whether parasite carriage affects innate immune cell responses in vitro to P. falciparum infected red blood cells (PfRBC).

Methods: Peripheral blood mononuclear cells were collected from 61 Malian children aged 5 to 15 years at the start of the transmission season. Parasite carriage at the start of the transmission season was assessed by PCR and microscopy for Malian children. Peripheral blood mononuclear cells were stimulated with PfRBC to assess cytokine production and degranulation of innate lymphocytes (γδ T-cells, CD3+CD56+ cells and NK cells) by flow cytometry.

Results: Granzyme B production in response to PfRBC was observed by all three innate cell subsets in Malian children, as were IFNγ production by γδ T-cells and NK cells and γδ T-cell degranulation. Children with ongoing P. falciparum infection showed significantly reduced PfRBC-specific IFNγ production by γδ T-cells and NK cells and degranulation by γδ T-cells as compared with those with undetectable parasitaemia by PCR and microscopy. Reduced IFNγ responses by NK cells were already observed for children with submicroscopic parasitaemia as compared to those with negative PCR. Children with high parasite densities showed a significant reduction in degranulating γδ T-cells relative to their low parasite density counterparts.

Conclusion: P. falciparum-specific responses by γδ T-cells and NK cells were negatively impacted by ongoing P. falciparum infection.