Group B Streptococcal Membrane Vesicles Induce Proinflammatory Cytokine Production and Are Sensed in an NLRP3 Inflammasome-Dependent Mechanism in a Human Macrophage-like Cell Line.

Group B (GBS) is a major cause of fetal and neonatal mortality worldwide. Many of the adverse effects of invasive GBS are associated with inflammation; therefore, understanding bacterial factors that promote inflammation is of critical importance. Membrane vesicles (MVs), which are produced by many bacteria, may modulate host inflammatory responses.

Changes in thyroid hormone concentrations over time in dogs with autoimmune thyroiditis.

Objective: The objective of this study was to follow long-term changes in the concentration of thyroid hormones in dogs with subclinical thyroiditis.

Samples: Samples were obtained from 125 dogs with subclinical thyroiditis. The study population included 70 female and 55 male dogs.

HPV+ head and neck cancer-derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain.

Severe pain is often experienced by patients with head and neck cancer and is associated with a poor prognosis. Despite its frequency and severity, current treatments fail to adequately control cancer-associated pain because of our lack of mechanistic understanding. Although recent works have shed some light of the biology underlying pain in HPV-negative oral cancers, the mechanisms mediating pain in HPV+ cancers remain unknown.

Co-alterations of circadian clock gene transcripts in human placenta in preeclampsia.

Pre-eclampsia (PE) is a hypertensive condition that occurs during pregnancy and complicates up to 4% of pregnancies. PE exhibits several circadian-related characteristics, and the placenta possesses a functioning molecular clock. We examined the associations of 17 core circadian gene transcripts in placenta with PE vs.

Impact of Estrogen and Progesterone on Immune Cells and Host-Pathogen Interactions in the Lower Female Reproductive Tract.

Microbial infections are a threat to women's reproductive health. Although reproductive cycles and pregnancy are controlled by sex hormones, the impact of hormones on host-pathogen interactions and immune function in the female reproductive tract are understudied. Furthermore, the changing endocrine environment throughout pregnancy may influence how and when women are susceptible to ascending infection.

Isolation and characterization of uterine leukocytes collected using a uterine swab technique.

Problem: Leukocytes from the maternal-fetal interface are a valuable tool to study local changes in immune function during pregnancy; however, sampling can be challenging due to inadequate tissue availability and the invasive nature of placental bed biopsy. Here, we aim to purify and characterize leukocytes from paired peripheral and uterine blood samples to assess whether a less invasive method of uterine blood collection could yield a population of enriched uterine leukocytes suitable for ex vivo and in vitro analyses.

Method Of Study: Human peripheral blood mononuclear cells (PBMC) and uterine blood mononuclear cells (UBMC) expressed from surgical gauze post C-section were isolated, and immunophenotypic information was acquired by multi-parameter flow cytometry.

Corrigendum: Nuclear Progesterone Receptor Expressed by the Cortical Thymic Epithelial Cells Dictates Thymus Involution in Murine Pregnancy.

[This corrects the article DOI: 10.3389/fendo.2022.

Endometrial Epithelial ARID1A Is Required for Uterine Immune Homeostasis during Early Pregnancy.

A growing body of work suggests epigenetic dysregulation contributes to endometriosis pathophysiology and female infertility. The chromatin remodeling complex subunit AT-rich interaction domain 1A (ARID1A) must be properly expressed to maintain normal uterine function. Endometrial epithelial ARID1A is indispensable for pregnancy establishment in mice through regulation of endometrial gland function; however, ARID1A expression is decreased in infertile women with endometriosis.

Fetal-placental antigens and the maternal immune system: Reproductive immunology comes of age.

Reproductive physiology and immunology as scientific disciplines each have rich, largely independent histories. The physicians and philosophers of ancient Greece made remarkable observations and inferences to explain regeneration as well as illness and immunity. The scientific enlightenment of the renaissance and the technological advances of the past century have led to the explosion of knowledge that we are experiencing today.

Nuclear Progesterone Receptor Expressed by the Cortical Thymic Epithelial Cells Dictates Thymus Involution in Murine Pregnancy.

Progesterone is a gonadal pro-gestational hormone that is absolutely necessary for the success of pregnancy. Most notable actions of progesterone are observed in the female reproductive organs, the uterus and the ovary. Acting through the nuclear progesterone receptor (PGR), progesterone prepares the endometrium for implantation of the embryo.

Production and Composition of Group B Streptococcal Membrane Vesicles Vary Across Diverse Lineages.

Although the neonatal and fetal pathogen Group B (GBS) asymptomatically colonizes the vaginal tract of ∼30% of pregnant women, only a fraction of their offspring develops invasive disease. We and others have postulated that these dimorphic clinical phenotypes are driven by strain variability; however, the bacterial factors that promote these divergent clinical phenotypes remain unclear. It was previously shown that GBS produces membrane vesicles (MVs) that contain active virulence factors capable of inducing adverse pregnancy outcomes.

Multiple Lesions Contribute to Infertility in Males Lacking Autoimmune Regulator.

Male factors, including those of autoimmune origin, contribute to approximately 50% of infertility cases in humans. However, the mechanisms underlying autoimmune male infertility are poorly understood. Deficiency in autoimmune regulator (AIRE) impairs central immune tolerance because of diminished expression of self-antigens in the thymus.

Bisphenol S and Epidermal Growth Factor Receptor Signaling in Human Placental Cytotrophoblasts.

Background: Bisphenol S (BPS) is an endocrine-disrupting chemical and the second most abundant bisphenol detected in humans. BPS exposure leads to reduced binucleate cell number in the ovine placenta. Binucleate cells form by cellular fusion, similar to the human placental syncytiotrophoblast layer.

Integrins mediate placental extracellular vesicle trafficking to lung and liver in vivo.

Membrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication. Here, we aimed to identify maternal cells targeted by placental EVs and elucidate the mechanisms by which they traffic to these cells. Exogenously administered pregnancy-associated EVs traffic specifically to the lung; further, placental EVs associate with lung interstitial macrophages and liver Kupffer cells in an integrin-dependent manner.

Distinct Group B Sequence and Capsule Types Differentially Impact Macrophage Stress and Inflammatory Signaling Responses.

Group B (GBS) is an opportunistic bacterial pathogen that can contribute to the induction of preterm birth in colonized pregnant women and to severe neonatal disease. Many questions regarding the mechanisms that drive GBS-associated pathogenesis remain unanswered, and it is not yet clear why virulence has been observed to vary so extensively across GBS strains. Previously, we demonstrated that GBS strains of different sequence types (STs) and capsule (CPS) types induce different cytokine profiles in infected THP-1 macrophage-like cells.

Exploring the Origin and Antigenic Specificity of Maternal Regulatory T Cells in Pregnancy.

Successful pregnancy outcome is partially determined by the suppression of reactive effector T cells by maternal regulatory T cells (T) at the maternal-fetal interface. While a large area of research has focused on the regulation of peripherally-induced T (pT) distribution and differentiation using transgenic mouse models and human samples, studies focusing on the role of T derived from the thymus (tT), and the potential role of central tolerance in maternal-fetal tolerance is less explored. The genome of the fetus is composed of both the tissue-specific and paternally-inherited antigens, and a break in maternal immune tolerance to either antigen may result in adverse pregnancy outcomes.

Modulation of Death and Inflammatory Signaling in Decidual Stromal Cells following Exposure to Group B .

Group B (GBS) is an opportunistic bacterial pathogen that contributes to miscarriage, preterm birth, and serious neonatal infections. Studies have indicated that some multilocus sequence types (STs) of GBS are more likely to cause severe disease than others. We hypothesized that the ability of GBS to elicit varying host responses in maternal decidual tissue during pregnancy is an important factor regulating infection and disease severity.

Genetically distinct Group B Streptococcus strains induce varying macrophage cytokine responses.

Group B Streptococcus (GBS) is an opportunistic pathogen that causes preterm birth and neonatal disease. Although GBS is known to exhibit vast diversity in virulence across strains, the mechanisms of GBS-associated pathogenesis are incompletely understood. We hypothesized that GBS strains of different genotypes would vary in their ability to elicit host inflammatory responses, and that strains associated with neonatal disease would induce different cytokine profiles than those associated with colonization.

Maternal alloimmune IgG causes anti-glomerular basement membrane disease in perinatal transgenic mice that express human laminin α5.

Mammalian immune systems are not mature until well after birth. However, transfer of maternal IgG to the fetus and newborn usually provides immunoprotection from infectious diseases. IgG transfer occurs before birth in humans across the placenta and continues after birth across the intestine in many mammalian species, including rodents.

Quantifying murine placental extracellular vesicles across gestation and in preterm birth data with tidyNano: A computational framework for analyzing and visualizing nanoparticle data in R.

Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication that carry protein, lipids, and nucleic acids via the circulation to target cells whereupon they mediate physiological changes. In pregnancy, EVs are released in high quantities from the placenta and have been postulated to target multiple cell types, including those of the vascular and immune systems. However, most studies of pregnancy-associated EVs have used clinical samples and in vitro models; to date, few studies have taken advantage of murine models in which pregnancy can be precisely timed and manipulated.

Autoimmune Regulator is required in female mice for optimal embryonic development and implantation†.

Autoimmune Regulator (AIRE) regulates central immune tolerance by inducing expression of tissue-restricted antigens in thymic medullary epithelial cells, thereby ensuring elimination of autoreactive T cells. Aire mutations in humans and targeted Aire deletion in mice result in multiorgan autoimmune disease, known in humans as autoimmune polyglandular syndrome type 1 (APS-1). APS-1 is characterized by the presence of adrenal insufficiency, chronic mucosal candidiasis, and/or hypoparathyroidism.

Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta.

Differentiation of first trimester human placental cytotrophoblast (CTB) from an anchorage-dependent epithelial phenotype into the mesenchymal-like invasive extravillous trophoblast (EVT) is crucial in the development of the maternal-fetal interface. We showed previously that differentiation of first trimester CTB to EVT involves an epithelial-mesenchymal transition (EMT). Here we compare the epithelial-mesenchymal characteristics of CTB and EVT derived from normal third trimester placenta or placenta previa versus abnormally invasive placenta (AIP).

IFPA meeting 2016 workshop report III: Decidua-trophoblast interactions; trophoblast implantation and invasion; immunology at the maternal-fetal interface; placental inflammation.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of decidual-trophoblast interaction, regulation of trophoblast invasion, immune cells at the maternal-fetal interface, and placental inflammation.

Immune response to a model shared placenta/tumor-associated antigen reduces cancer risk in parous mice.

During human pregnancy, paternally inherited antigens expressed by the fetal-placental unit can elicit expansion of antigen-specific CD8+ T cells. These cells can persist for years as memory T cells, but their effects on long-term maternal health are unknown. Shared placenta/tumor-associated antigens are expressed by placenta and tumors, but are minimally expressed or absent in normal adult tissues.