A novel population of memory-activated natural killer cells associated with low parasitaemia in Plasmodium falciparum-exposed sickle-cell trait children

Loiseau, Claire, Doumbo, Ogobara K, Traore, Boubacar, Brady, Jamie L., Proietti, Carla, de Sousa, Katrina P., Crompton, Peter D., and Doolan, Denise L. (2020) A novel population of memory-activated natural killer cells associated with low parasitaemia in Plasmodium falciparum-exposed sickle-cell trait children. Clinical & Translational Immunology, 9 (4). 1125.

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Abstract

Objectives. The sickle-cell trait phenotype is associated with protection from malaria. Multiple molecular mechanisms have been proposed to explain this protection, but the role of the host immune system has been poorly investigated. We hypothesised that cellular immunity to malaria may develop differently in sicklecell trait children (HbAS) and children with normal haemoglobin (HbAA) repeatedly exposed to Plasmodium falciparum (Pf). Methods. Paired samples collected prior to the Pf transmission season and during the first malaria episode of the ensuing transmission season from HbAS and HbAA children were analysed by multiplex bead-based assay and comprehensive multidimensional flow cytometry profiling. Results. Cellular immune profiles were enriched in HbAS relative to HbAA children before the start of the Pf transmission season, with a distinct NK subset. These cells were identified as a novel subset of memory-activated NK cells characterised by reduced expression of the ecto-enzyme CD38 as well as co-expression of high levels of HLA-DR and CD45RO. The frequency of this NK subset before the transmission season was negatively correlated with parasite density quantified during the first malaria episode of the ensuing transmission season. Functional assessment revealed that these CD38dim CD45RO+ HLA-DR+ NK cells represent a important source of IFN-c. Conclusion. Our data suggest that this novel memory-activated NK cell subset may contribute to an accelerated and enhanced IFN-cmediated immune response and to control of parasite density in individuals with the sickle-cell trait. This distinct cellular immune profile may contribute to predispose HbAS children to a relative protection from malaria.

Item ID: 62745
Item Type: Article (Research - C1)
ISSN: 2050-0068
Keywords: haemoglobin AS, natural killer cells, parasite burden, Plasmodium falciparum, protective immunity, sickle-cell trait phenotype
Copyright Information: © 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC program grant 1132975, NHMRC principal fellowship 1137285
Date Deposited: 18 May 2020 22:27
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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