Association of Inhibitory Killer Cell Immunoglobulin-like Receptor Ligands With Higher Plasmodium falciparum Parasite Prevalence
Association of Inhibitory Killer Cell Immunoglobulin-like Receptor Ligands With Higher Plasmodium falciparum Parasite Prevalence
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DOI：
10.1093/infdis/jiaa698
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发表时间：
2021-07-01
影响因子：
6.4
通讯作者：
Feeney, Margaret E.
中科院分区：
文献类型：
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作者：
Digitale, Jean C.;Callaway, Perri C.;Feeney, Margaret E.
杀伤细胞免疫球蛋白样受体 (KIR) 及其 HLA 配体影响许多传染病的结果。我们在 890 名乌干达个体的纵向队列中分析了复合 K1R-HLA 基因型与恶性疟原虫感染风险的关系。我们发现，HLA-C2 和 HLA-Bw4（分别是抑制性 KIR2DL1 和 KIR3DL1 的配体）的存在，以相加的方式增加了恶性疟原虫血症的可能性。 HLA-C2 纯合子通过 KIR2DL1 介导较强的抑制作用，发生寄生虫血症的几率最高，HLA-C1/C2 杂合子的发生几率中等，而 HLA-C1 纯合子通过 KIR2DL2/3 介导较弱的抑制作用，发生寄生虫血症的几率最低。此外，HLA-C（抑制性 KIR2DL1/2/3 的配体）表面表达较高，与寄生虫血症的可能性较高相关。这些数据共同表明，更强的 KIR 介导的抑制会导致更高的恶性疟原虫血症风险，并表明表达 KIR 的效应细胞在介导抗寄生虫免疫中发挥作用。
Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands influence the outcome of many infectious diseases. We analyzed the relationship of compound K1R-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.