Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.
Department of Medicine, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.
Sci Rep. 2021 Feb 18;11(1):4130. doi: 10.1038/s41598-021-83093-4.
Immune effector responses against Plasmodium falciparum include antibody-mediated activation of innate immune cells, which can induce Fc effector functions, including antibody-dependent cellular cytotoxicity, and the secretion of cytokines and chemokines. These effector functions are regulated by the composition of immunoglobulin G (IgG) Fc N-linked glycans. However, a role for antibody-mediated natural killer (NK) cells activation or Fc N-linked glycans in pregnant women with malaria has not yet been established. Herein, we studied the capacity of IgG antibodies from pregnant women, with placental malaria or non-placental malaria, to induce NK cell activation in response to placental malaria-associated antigens DBL2 and DBL3. Antibody-mediated NK cell activation was observed in pregnant women with malaria, but no differences were associated with susceptibility to placental malaria. Elevated anti-inflammatory glycosylation patterns of IgG antibodies were observed in pregnant women with or without malaria infection, which were not seen in healthy non-pregnant controls. This suggests that pregnancy-associated anti-inflammatory Fc N-linked glycans may dampen the antibody-mediated activation of NK cells in pregnant women with malaria infection. Overall, although anti-inflammatory glycans and antibody-dependent NK cell activation were detected in pregnant women with malaria, a definitive role for these antibody features in protecting against placental malaria remains to be proven.
针对疟原虫的免疫效应反应包括抗体介导的固有免疫细胞激活，这可以诱导 Fc 效应功能，包括抗体依赖的细胞毒性和细胞因子和趋化因子的分泌。这些效应功能受免疫球蛋白 G (IgG) Fc N-连接糖基化的组成调节。然而，抗体介导的自然杀伤 (NK) 细胞激活或 Fc N-连接糖基化在患有疟疾的孕妇中的作用尚未确定。在此，我们研究了来自患有胎盘疟疾或非胎盘疟疾的孕妇的 IgG 抗体诱导 NK 细胞针对胎盘疟疾相关抗原 DBL2 和 DBL3 激活的能力。在患有疟疾的孕妇中观察到了抗体介导的 NK 细胞激活，但与胎盘疟疾的易感性无关。在患有或不患有疟疾感染的孕妇中观察到升高的抗炎性 IgG 抗体糖基化模式，而在健康的非妊娠对照中则没有观察到。这表明与妊娠相关的抗炎性 Fc N-连接糖基可能会抑制患有疟疾感染的孕妇中抗体介导的 NK 细胞激活。总的来说，尽管在患有疟疾的孕妇中检测到抗炎性聚糖和抗体依赖性 NK 细胞激活，但这些抗体特征在预防胎盘疟疾中的明确作用仍有待证明。
