Decidual NK cells kill Zika virus-infected trophoblasts.
Sumit Sen SantaraÂngela C CrespoSachin MulikCristian OviesSelma BoulenouarJack L StromingerJudy LiebermanPublished in: Proceedings of the National Academy of Sciences of the United States of America (2021)
Zika virus (ZIKV) during pregnancy infects fetal trophoblasts and causes placental damage and birth defects including microcephaly. Little is known about the anti-ZIKV cellular immune response at the maternal-fetal interface. Decidual natural killer cells (dNK), which directly contact fetal trophoblasts, are the dominant maternal immune cells in the first-trimester placenta, when ZIKV infection is most hazardous. Although dNK express all the cytolytic molecules needed to kill, they usually do not kill infected fetal cells but promote placentation. Here, we show that dNK degranulate and kill ZIKV-infected placental trophoblasts. ZIKV infection of trophoblasts causes endoplasmic reticulum (ER) stress, which makes them dNK targets by down-regulating HLA-C/G, natural killer (NK) inhibitory receptor ligands that help maintain tolerance of the semiallogeneic fetus. ER stress also activates the NK activating receptor NKp46. ZIKV infection of Ifnar1 -/- pregnant mice results in high viral titers and severe intrauterine growth restriction, which are exacerbated by depletion of NK or CD8 T cells, indicating that killer lymphocytes, on balance, protect the fetus from ZIKV by eliminating infected cells and reducing the spread of infection.
Keyphrases
- zika virus
- nk cells
- dengue virus
- aedes aegypti
- induced apoptosis
- immune response
- endoplasmic reticulum
- cell cycle arrest
- natural killer cells
- oxidative stress
- signaling pathway
- physical activity
- pregnancy outcomes
- pregnant women
- type diabetes
- sars cov
- inflammatory response
- peripheral blood
- body mass index
- toll like receptor
- endoplasmic reticulum stress
- cell death
- high fat diet induced