Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection

Rebecca Kotzur, Shira Kahlon, Batya Isaacson, Moriya Gamliel, Yoav Charpak-Amikam, Judy Lieberman, Gilad Bachrach, Debra Goldman-Wohl, Simcha Yagel, Ofer Beharier, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Natural killer cells (NKs) found during pregnancy at the maternal-fetal interface named decidual (d)NKs, show signs of education following first pregnancy, resulting in better placentation and fetus-growth, hence termed pregnancy trained dNKs (PTdNKs). Here we show that PTdNKs provide increased protection of the fetus from Fusobacterium nucleatum (FN) infection. We demonstrate that PTdNKs secrete elevated amounts of the bacteriocidal protein granulysin (GNLY) upon incubation with FN compared to dNKs derived from first pregnancies, which leads to increased killing of FN. Furthermore, we showed mechanistically that the GNLY secretion is mediated through the interaction of the FN’s Fap2 protein with Gal-GalNAc present on PTdNKs. Finally, we show in vivo, using GNLY-tg mice that enhanced protection of the fetuses from FN infection is observed, as compared to wild type and that this enhance protection is NK cell dependent. Altogether, we show a new function for PTdNKs as protectors of the fetus from bacterial infection.

Original languageAmerican English
Article numbere1011923
JournalPLoS Pathogens
Volume20
Issue number1
DOIs
StatePublished - Jan 2024

Bibliographical note

Publisher Copyright:
Copyright: © 2024 Kotzur et al.

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