Antibody mediated activation of natural killer cells in malaria exposed pregnant women

Timon Damelang, Elizabeth H. Aitken, Wina Hasang, Ester Lopez, Martin Killian, Holger W. Unger, Ali Salanti, Alexis Shub, Elizabeth McCarthy, Katherine Kedzierska, Martha Lappas, Stephen J. Kent, Stephen J. Rogerson, Amy W. Chung

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Abstract

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.

Original languageEnglish
Article number4130
Pages (from-to)1-16
Number of pages16
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - 18 Feb 2021

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