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

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 prot...

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Main Authors: Rebecca Kotzur, Shira Kahlon, Batya Isaacson, Moriya Gamliel, Yoav Charpak-Amikam, Judy Lieberman, Gilad Bachrach, Debra Goldman-Wohl, Simcha Yagel, Ofer Beharier, Ofer Mandelboim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1011923
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author Rebecca Kotzur
Shira Kahlon
Batya Isaacson
Moriya Gamliel
Yoav Charpak-Amikam
Judy Lieberman
Gilad Bachrach
Debra Goldman-Wohl
Simcha Yagel
Ofer Beharier
Ofer Mandelboim
author_facet Rebecca Kotzur
Shira Kahlon
Batya Isaacson
Moriya Gamliel
Yoav Charpak-Amikam
Judy Lieberman
Gilad Bachrach
Debra Goldman-Wohl
Simcha Yagel
Ofer Beharier
Ofer Mandelboim
author_sort Rebecca Kotzur
collection DOAJ
description 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.
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language English
publishDate 2024-01-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-5c3bbb7d66694b8dad23a0761ddb0b9d2025-08-20T02:11:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-01-01201e101192310.1371/journal.ppat.1011923Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection.Rebecca KotzurShira KahlonBatya IsaacsonMoriya GamlielYoav Charpak-AmikamJudy LiebermanGilad BachrachDebra Goldman-WohlSimcha YagelOfer BeharierOfer MandelboimNatural 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.https://doi.org/10.1371/journal.ppat.1011923
spellingShingle Rebecca Kotzur
Shira Kahlon
Batya Isaacson
Moriya Gamliel
Yoav Charpak-Amikam
Judy Lieberman
Gilad Bachrach
Debra Goldman-Wohl
Simcha Yagel
Ofer Beharier
Ofer Mandelboim
Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection.
PLoS Pathogens
title Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection.
title_full Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection.
title_fullStr Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection.
title_full_unstemmed Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection.
title_short Pregnancy trained decidual NK cells protect pregnancies from harmful Fusobacterium nucleatum infection.
title_sort pregnancy trained decidual nk cells protect pregnancies from harmful fusobacterium nucleatum infection
url https://doi.org/10.1371/journal.ppat.1011923
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