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

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2020 Nov 9

PMID 33165540

Citations 7

Authors

Jean C Digitale

Perri C Callaway

Maureen Martin

George Nelson

Mathias Viard

John Rek

Emmanuel Arinaitwe

Grant Dorsey

Moses Kamya

Mary Carrington

Isabel Rodriguez-Barraquer

Margaret E Feeney

Affiliations

Soon will be listed here.

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.

Citing Articles

An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania.

Loh L, Saunders P, Faoro C, Font-Porterias N, Nemat-Gorgani N, Harrison G Cell. 2024; 187(24):7008-7024.e19.

PMID: 39476840 PMC: 11606752. DOI: 10.1016/j.cell.2024.10.005.

Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria.

Ty M, Sun S, Callaway P, Rek J, Press K, van der Ploeg K Sci Transl Med. 2023; 15(680):eadd9012.

PMID: 36696483 PMC: 9976268. DOI: 10.1126/scitranslmed.add9012.

Genetic variation that determines expression levels associates with the course of malaria in an HLA allotype-dependent manner.

Walker-Sperling V, Digitale J, Viard M, Martin M, Bashirova A, Yuki Y Proc Natl Acad Sci U S A. 2022; 119(29):e2205498119.

PMID: 35858344 PMC: 9303992. DOI: 10.1073/pnas.2205498119.

Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health.

Pollock N, Harrison G, Norman P J Allergy Clin Immunol Pract. 2022; 10(7):1763-1775.

PMID: 35561968 PMC: 10038757. DOI: 10.1016/j.jaip.2022.04.036.

Allele imputation for the killer cell immunoglobulin-like receptor KIR3DL1/S1.

Harrison G, Leaton L, Harrison E, Kichula K, Viken M, Shortt J PLoS Comput Biol. 2022; 18(2):e1009059.

PMID: 35192601 PMC: 8896733. DOI: 10.1371/journal.pcbi.1009059.

References

Kulkarni S, Martin M, Carrington M . The Yin and Yang of HLA and KIR in human disease. Semin Immunol. 2008; 20(6):343-52. PMC: 3501819. DOI: 10.1016/j.smim.2008.06.003. View

Dantzler K, Jagannathan P . γδ T Cells in Antimalarial Immunity: New Insights Into Their Diverse Functions in Protection and Tolerance. Front Immunol. 2018; 9:2445. PMC: 6206268. DOI: 10.3389/fimmu.2018.02445. View

Moras M, Lefevre S, Ostuni M . From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals. Front Physiol. 2018; 8:1076. PMC: 5742207. DOI: 10.3389/fphys.2017.01076. View

Rodriguez-Barraquer I, Arinaitwe E, Jagannathan P, Kamya M, Rosenthal P, Rek J . Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure. Elife. 2018; 7. PMC: 6103767. DOI: 10.7554/eLife.35832. View

Sturm A, Amino R, van de Sand C, Regen T, Retzlaff S, Rennenberg A . Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science. 2006; 313(5791):1287-90. DOI: 10.1126/science.1129720. View

Hirayasu K, Ohashi J, Kashiwase K, Hananantachai H, Naka I, Ogawa A . Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA. PLoS Pathog. 2012; 8(3):e1002565. PMC: 3297587. DOI: 10.1371/journal.ppat.1002565. View

Suscovich T, Fallon J, Das J, Demas A, Crain J, Linde C . Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination. Sci Transl Med. 2020; 12(553). DOI: 10.1126/scitranslmed.abb4757. View

Single R, Martin M, Meyer D, Gao X, Carrington M . Methods for assessing gene content diversity of KIR with examples from a global set of populations. Immunogenetics. 2008; 60(12):711-25. PMC: 2663517. DOI: 10.1007/s00251-008-0331-1. View

Kamya M, Arinaitwe E, Wanzira H, Katureebe A, Barusya C, Kigozi S . Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control. Am J Trop Med Hyg. 2015; 92(5):903-12. PMC: 4426576. DOI: 10.4269/ajtmh.14-0312. View

10.

Middleton D, Gonzelez F . The extensive polymorphism of KIR genes. Immunology. 2009; 129(1):8-19. PMC: 2807482. DOI: 10.1111/j.1365-2567.2009.03208.x. View

11.

Zaidi I, Diallo H, Conteh S, Robbins Y, Kolasny J, Orr-Gonzalez S . γδ T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations. J Immunol. 2017; 199(11):3781-3788. PMC: 5698172. DOI: 10.4049/jimmunol.1700314. View

12.

Naiyer M, Cassidy S, Magri A, Cowton V, Chen K, Mansour S . KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C. Sci Immunol. 2017; 2(15). DOI: 10.1126/sciimmunol.aal5296. View

13.

Martin M, Carrington M . KIR locus polymorphisms: genotyping and disease association analysis. Methods Mol Biol. 2008; 415:49-64. PMC: 10763752. DOI: 10.1007/978-1-59745-570-1_3. View

14.

Tran T, Li S, Doumbo S, Doumtabe D, Huang C, Dia S . An intensive longitudinal cohort study of Malian children and adults reveals no evidence of acquired immunity to Plasmodium falciparum infection. Clin Infect Dis. 2013; 57(1):40-7. PMC: 3669526. DOI: 10.1093/cid/cit174. View

15.

Nakimuli A, Chazara O, Farrell L, Hiby S, Tukwasibwe S, Knee O . Killer cell immunoglobulin-like receptor (KIR) genes and their HLA-C ligands in a Ugandan population. Immunogenetics. 2013; 65(11):765-75. PMC: 3824577. DOI: 10.1007/s00251-013-0724-7. View

16.

Khakoo S, Thio C, Martin M, Brooks C, Gao X, Astemborski J . HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science. 2004; 305(5685):872-4. DOI: 10.1126/science.1097670. View

17.

Farrington L, Callaway P, Vance H, Baskevitch K, Lutz E, Warrier L . Opsonized antigen activates Vδ2+ T cells via CD16/FCγRIIIa in individuals with chronic malaria exposure. PLoS Pathog. 2020; 16(10):e1008997. PMC: 7605717. DOI: 10.1371/journal.ppat.1008997. View

18.

WINTER C, Gumperz J, Parham P, Long E, Wagtmann N . Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. J Immunol. 1998; 161(2):571-7. View

19.

Mamedov M, Scholzen A, Nair R, Cumnock K, Kenkel J, Oliveira J . A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence. Immunity. 2018; 48(2):350-363.e7. PMC: 5956914. DOI: 10.1016/j.immuni.2018.01.009. View

20.

Arora G, Hart G, Manzella-Lapeira J, Doritchamou J, Narum D, Thomas L . NK cells inhibit growth in red blood cells via antibody-dependent cellular cytotoxicity. Elife. 2018; 7. PMC: 6019063. DOI: 10.7554/eLife.36806. View