Decidual NK Cells Transfer Granulysin to Selectively Kill Bacteria in Trophoblasts

Maternal natural killer cells at the intersection between reproduction and mucosal immunity

“…Also, humanized mouse models can be applied to study P. falciparum ; however, it is still unknow how well these models represent P. falciparum infection - associated pathophysiology INFɣ-mediated decrease of parasite load (comparison between WT and Ifnɣ −/ − mice; also, results (correlation only) from observational study on humans) 130 , 136 NK*, pbNK* INFɣ-mediated miscarriage (comparison between WT and Ifnɣ −/ − mice) 136 NK* Listeria monocytogenes Higher susceptibility to listeriosis in pregnant individuals, pregnancy loss, preterm birth, stillbirth, vertical transmission and congenital diseases Listeriosis is a natural infection for rodents; however, susceptibility to L. monocytogenes varies a lot between different strains of mice. Spontaneous abortion (resorption), placentitis, placental necrosis, endometritis, stillbirth and vertical transmission are described for listeriosis in mice, but mechanisms of the placental barrier crossing differ between WT mice and humans Killing of L. monocytogenes by injecting anti-microbial pertide granulysin through nanotubes to infected cells 148 dNK, pbNK Hepatitis C Virus (HCV) Vertical transmission Mice are not susceptible to HCV. There are xenograft and humanized mouse models, but they are designed to study liver disease and not pregnancy outcomes; therefore, they are not suitable for mother-to-fetus transmission – Human Immunodeficiency Virus (HIV) Vertical transmission, infants born from HIV-positive women are at higher risk of intrauterine FGR and low birth weight Mice are not susceptible to HIV.…”

“… 146 However, very recently, dNK cells were shown to kill L. monocytogenes from within EVT, by injecting anti-microbial Granulysin through nanotubes. 148 …”

“…However, temporal changes in the frequencies of the two types of cells in the decidua suggest that tissue-resident T cells may be more important in late gestation, while NK cells may specialize in certain defense mechanisms, like the recently reported nanotube-mediated transfer of granulysin into Listeria-infected trophoblast. 148 Decidual CD8 + T cells are able to degranulate and produce pro-inflammatory cytokines in response to stimulation and are therefore competent in their response to pathogen invasion. 319 How decidual NK and T cells operate during infections and which cells they interact with can be inferred by looking at the sets of MHC class I molecules expressed on cells in the decidua.…”

Do endometrial natural killer and regulatory T cells differ in infertile and clinical pregnancy patients? An analysis in patients undergoing frozen embryo transfer cycles

“…37 One limitation of their analysis was that they did not in- cells in their infertile or RPL group compared to fertile controls. 18,38 The CD16 cell surface receptor on NK cells activates the antibody dependent cell-mediated cytotoxicity (ADCC) and is important for the innate immune response. uNK cells have reduced cytotoxicity levels compared to peripheral blood NK cells and typically downregulate their CD16 receptor.…”

“…For example, uNK cells which produce granulysin may have double-edged effects on pregnancy. 17,18 It is also hypothesized that women with infertility have a higher percentage of CD16 + uNK cells compared with fertile women and that evaluating CD56 + uNK cells alone may not be diagnostic. 13,14 Another immune cell type that may be involved in embryo implantation is the specialized population of regulatory T cells (Treg).…”