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. 2021 Jul 2;224(1):175-183.
doi: 10.1093/infdis/jiaa698.

Association of Inhibitory Killer Cell Immunoglobulin-like Receptor Ligands With Higher Plasmodium falciparum Parasite Prevalence

Jean C Digitale  1   2 , Perri C Callaway  1   3 , Maureen Martin  4 , George Nelson  5 , Mathias Viard  4 , John Rek  6 , Emmanuel Arinaitwe  6   7 , Grant Dorsey  1 , Moses Kamya  6   8 , Mary Carrington  4   9 , Isabel Rodriguez-Barraquer  1 , Margaret E Feeney  1   10
Affiliations

Association of Inhibitory Killer Cell Immunoglobulin-like Receptor Ligands With Higher Plasmodium falciparum Parasite Prevalence

Jean C Digitale et al. J Infect Dis. .

Abstract

Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands influence the outcome of many infectious diseases. We analyzed the relationship of compound KIR-HLA genotypes with risk of Plasmodium falciparum infection in a longitudinal cohort of 890 Ugandan individuals. We found that presence of HLA-C2 and HLA-Bw4, ligands for inhibitory KIR2DL1 and KIR3DL1, respectively, increased the likelihood of P. falciparum parasitemia in an additive manner. Individuals homozygous for HLA-C2, which mediates strong inhibition via KIR2DL1, had the highest odds of parasitemia, HLA-C1/C2 heterozygotes had intermediate odds, and individuals homozygous for HLA-C1, which mediates weaker inhibition through KIR2DL2/3, had the lowest odds of parasitemia. In addition, higher surface expression of HLA-C, the ligand for inhibitory KIR2DL1/2/3, was associated with a higher likelihood of parasitemia. Together these data indicate that stronger KIR-mediated inhibition confers a higher risk of P. falciparum parasitemia and suggest that KIR-expressing effector cells play a role in mediating antiparasite immunity.

Keywords: HLA; KIR; NK cells; Plasmodium falciparum; malaria.

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