Converging cytokine and metabolite networks shape asymmetric T cell fate at the term human maternal-fetal interface.

Placentation presents immune conflict between mother and fetus, yet in normal pregnancy maternal immunity against infection is maintained without expense to fetal tolerance. This is believed to result from adaptations at the maternal-fetal interface (MFI) which affect T cell programming, but the identities (i.e.

Adult-Onset Still's Disease in Pregnancy: Lessons Learned and an Approach to Subsequent Pregnancies.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disorder with potential for life-threatening complications in pregnancy. Recently, biologic therapeutics have been increasingly used for treatment of AOSD, but there is little available data on the treatment of AOSD in pregnancy. Here we report a 23-year-old primigravid patient with a history of AOSD who presented at 20 weeks of gestation with fever, arthralgias, rash, fatigue, and highly elevated ferritin, concerning for AOSD flare.

Increased fetal microchimerism in immune and stem cell subsets in preeclampsia.

Problem: Preeclampsia (PE) is associated with an increased risk of maternal cardiovascular disease (CVD), however, it is unclear whether this is due to shared underlying physiology or changes which occur during the disease process. Fetal microchimerism (FMc) within the maternal circulation can durably persist decades after pregnancy, is known to occur at greater frequency in PE, and can potentially affect local and systemic immune programming, thus changes in cellular FMc may provide a mechanism for long-term health outcomes associated with PE.

Method Of Study: We investigated whether PE is associated with alterations in FMc immune and stem cell populations.

Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State.

Background: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown.

Objective: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality.

Amniotic fluid interleukin 6 and interleukin 8 are superior predictors of fetal lung injury compared with maternal or fetal plasma cytokines or placental histopathology in a nonhuman primate model.

Background: Intra-amniotic infection or inflammation is common in early preterm birth and associated with substantial neonatal lung morbidity owing to fetal exposure to proinflammatory cytokines and infectious organisms. Amniotic fluid interleukin 8, a proinflammatory cytokine, was previously correlated with the development of neonatal bronchopulmonary dysplasia, but whether amniotic fluid cytokines or placental pathology more accurately predicts neonatal lung pathology and morbidity is unknown. We have used a pregnant nonhuman primate model of group B Streptococcus infection to study the pathogenesis of intra-amniotic infection, bacterial invasion of the amniotic cavity and fetus, and microbial-host interactions.

Human Tissue-Resident Memory T Cells in the Maternal-Fetal Interface. Lost Soldiers or Special Forces?

The immune system plays a critical role during pregnancy, but the specific mechanisms and immune cell function needed to support pregnancy remain incompletely understood. Despite decades of research efforts, it is still unclear how the immune system maintains tolerance of fetal-derived tissues, which include most cells of the placenta and of course the fetus itself, without forfeiting the ability to protect against harmful infections. T cells recognize antigen in the context of major histocompatibility complex (MHC) encoded proteins, but classical MHC class I and II expression are diminished in fetal-derived cells.

Obesity as a contributor to immunopathology in pregnant and non-pregnant adults with COVID-19.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to a global public health emergency with the need to identify vulnerable populations who may benefit from increased screening and healthcare resources. Initial data suggest that overall, pregnancy is not a significant risk factor for severe coronavirus disease 2019 (COVID-19). However, case series have suggested that maternal obesity is one of the most important comorbidities associated with more severe disease.

Clinical characteristics of 46 pregnant women with a severe acute respiratory syndrome coronavirus 2 infection in Washington State.

Background: The impact of coronavirus disease 2019 on pregnant women is incompletely understood, but early data from case series suggest a variable course of illness from asymptomatic or mild disease to maternal death. It is unclear whether pregnant women manifest enhanced disease similar to influenza viral infection or whether specific risk factors might predispose to severe disease.

Objective: To describe maternal disease and obstetrical outcomes associated with coronavirus disease 2019 in pregnancy to rapidly inform clinical care.

Etiology and workup of fevers in gynecologic oncology patients.

Objectives: The objectives of this study are to identify the characteristics of febrile gynecologic oncology patients and to evaluate the utility of common diagnostic procedures used to assess the etiologies of their fevers.

Methods/materials: Retrospective data were collected for 200 consecutive patients admitted to the gynecologic oncology service at 1 institution between January 2008 and December 2012 for a diagnosis of fever. Data were collected using contingency tables, and the χ test was used as appropriate.

Discussion: 'vitamin D deficiency in pregnancy and gestational diabetes,' by Burris et al.

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Burris HH, Rifas-Shiman SL, Kleinman K, et al. Vitamin D deficiency in pregnancy and gestational diabetes.

dsRNA sensors and plasmacytoid dendritic cells in host defense and autoimmunity.

The innate immune system detects viruses through molecular sensors that trigger the production of type I interferons (IFN-I) and inflammatory cytokines. As viruses vary tremendously in size, structure, genomic composition, and tissue tropism, multiple sensors are required to detect their presence in various cell types and tissues. In this review, we summarize current knowledge of the diversity, specificity, and signaling pathways downstream of viral sensors and ask whether two distinct sensors that recognize the same viral component are complementary, compensatory, or simply redundant.

TLR7/9 versus TLR3/MDA5 signaling during virus infections and diabetes.

IFN-I are pleiotropic cytokines that impact innate and adaptive immune responses. In this article, we discuss TLR7/9 versus TLR3/MDA5 signaling in antiviral responses and diabetes. pDCs are thought to have a critical role in antiviral defense because of their ability to rapidly secrete large amounts of IFN-I through TLR7/9 signaling.

Melanoma differentiation-associated protein-5 (MDA-5) limits early viral replication but is not essential for the induction of type 1 interferons after Coxsackievirus infection.

Coxsackievirus infections are associated with severe diseases such as myocarditis, meningitis and pancreatitis. To study the contribution of the intracellular viral sensor melanoma differentiation-associated protein-5 (MDA-5) in the host immune response to Coxsackievirus B3 (CVB3) we infected C57BL/6 and 129/SvJ mice lacking mda-5. Mice deficient in MDA-5 showed a dramatically increased susceptibility to CVB3 infection.

Viral sensors: diversity in pathogen recognition.

Innate sensors of viral infection detect viral products and initiate the signal cascades that lead to the antiviral response. Several proteins have been identified to play a role in this process, mostly members of the Toll-like receptor and retinoic acid-inducible gene I-like receptor families. These receptors have been demonstrated to function in part by recognizing a diverse yet unique repertoire of nucleic acid substrates.

MDA-5 recognition of a murine norovirus.

Noroviruses are important human pathogens responsible for most cases of viral epidemic gastroenteritis worldwide. Murine norovirus-1 (MNV-1) is one of several murine noroviruses isolated from research mouse facilities and has been used as a model of human norovirus infection. MNV-1 infection has been shown to require components of innate and adaptive immunity for clearance; however, the initial host protein that recognizes MNV-1 infection is unknown.

Chemical rescue of I-site cleavage in living cells and in vitro discriminates between the cytomegalovirus protease, assemblin, and its precursor, pUL80a.

Chemical rescue is an established approach that offers a directed strategy for designing mutant enzymes in which activity can be restored by supplying an appropriate exogenous compound. This method has been used successfully to study a broad range of enzymes in vitro, but its application to living systems has received less attention. We have investigated the feasibility of using chemical rescue to make a conditional-lethal mutant of the cytomegalovirus (CMV) maturational protease.