Inhibitory KIR ligands are associated with higher P. falciparum parasite prevalence

Author:

Digitale, Jean C

Callaway, Perri C

Martin, Maureen

Nelson,George

Viard,Mathias

Rek, John

Arinaitwe, Emmanuel

Dorsey, Grant

Kamya, Moses

Carrington,Mary

Rodriguez-Barraquer, Isabel

Feeney, Margaret E
Author Address

Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA., Infectious Disease and Immunity Graduate Group, University of California Berkeley, Berkeley, CA, USA., Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD, USA., Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD., Infectious Diseases Research Collaboration, Kampala, Uganda., London School of Hygiene and Tropical Medicine, London, United Kingdom., Department of Medicine, Makerere University, Kampala, Uganda., Ragon Institute of MGH MIT and Harvard, Cambridge, MA, USA., Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.,

Abstract:

Killer cell immunoglobulin-like receptors (KIR) 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. Additionally, 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 anti-parasite immunity. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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