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

Autor: Kotzur, Rebecca, Kahlon, Shira, Isaacson, Batya, Gamliel, Moriya, Charpak-Amikam, Yoav, Lieberman, Judy, Bachrach, Gilad, Goldman-Wohl, Debra, Yagel, Simcha, Beharier, Ofer, Mandelboim, Ofer
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Zdroj: PLoS Pathogens; 1/12/2024, Vol. 20 Issue 1, p1-16, 16p
Abstrakt: 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. Author summary: During this project, we aimed to elucidate the influence of natural killer (NK) cells in the protection of fetuses during pregnancy. At the maternal-fetal interface a special subset of NK cells can be found, the decidual NK (dNK) cells, which have been shown to be rather nurturing, in contrast to the cytotoxic peripheral blood NK cells. These cells are thought to be essential for the healthy development of placenta and fetus in the uterus. Bacterial and viral infections are quite common during pregnancy and pose a significant risk for the fetus and its development. In this manuscript, we describe how the dNK cells primed through first pregnancy show specific antibacterial properties against the bacterium Fusobacterium nucleatum via the lytic protein granulysin in contrast to the peripheral blood NK cells. Additionally, we showed that NK cells expressing granulysin in mice protect the developing fetuses from the effects of a maternal infection with the bacterium. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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