Obstetrics and Gynaecology - Research Publications

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Author: Aitken, Elizabeth × Author: Lappas, Martha × Author: McCarthy, Elizabeth × Author: Shub, Alexis × End date: 2022 × Start date: 2020 ×

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    Antibody mediated activation of natural killer cells in malaria exposed pregnant women
    Damelang, T ; Aitken, EH ; Hasang, W ; Lopez, E ; Killian, M ; Unger, HW ; Salanti, A ; Shub, A ; McCarthy, E ; Kedzierska, K ; Lappas, M ; Kent, SJ ; Rogerson, SJ ; Chung, AW (NATURE PORTFOLIO, 2021-02-18)
    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.