Distinct immune responses to HIV and CMV in Hofbauer cells across gestation highlight evolving placental immune dynamics.

Placental immune responses to Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (CMV) vary across gestational stages and may influence postnatal outcomes. This study investigates the innate immunity of Hofbauer cells from placentae obtained at early/mid-gestation (18-21.6 weeks) and term (>37 weeks).

Melatonin: the placental antioxidant and anti-inflammatory.

Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free radical scavenger, circadian rhythm regulator, and sleep hormone. However, its most popular role is the ability to regulate sleep through the circadian rhythm.

Machine learning to predict risk for community-onset Staphylococcus aureus infections in children living in southeastern United States.

Staphylococcus aureus (S. aureus) is known to cause human infections and since the late 1990s, community-onset antibiotic resistant infections (methicillin resistant S. aureus (MRSA)) continue to cause significant infections in the United States.

Host-Viral Interactions at the Maternal-Fetal Interface. What We Know and What We Need to Know.

In humans, the hemochorial placenta is a unique temporary organ that forms during pregnancy to support fetal development, gaseous exchange, delivery of nutrition, removal of waste products, and provides immune protection, while maintaining tolerance to the HLA-haploidentical fetus. In this review, we characterize decidual and placental immunity during maternal viral (co)-infection with HIV-1, human cytomegalovirus (HCMV), and Zika virus. We discuss placental immunology, clinical presentation, and epidemiology, before characterizing host susceptibility and cellular tropism, and how the three viruses gain access into specific placental target cells.

Feasibility and Acceptability of Technology-supported Sexual Health Education Among Adolescents Receiving Inpatient Psychiatric Care.

Mental illness in adolescence is associated with high-risk sexual behaviors including multiple sex partners, infrequent or inconsistent condom use, and nonuse of contraception. Inpatient psychiatric care represents a promising setting to provide sexual health education. This pilot study investigates the feasibility and acceptability of online sexual health education in this group by assessing usability and impact on short-term psychosocial outcomes.

Robust innate immune responses at the placenta during early gestation may limit in utero HIV transmission.

In 2019, >90% of new HIV infections in infants globally occurred vertically. Studies suggest intrauterine transmission most often occurs in the third trimester; however, there are no mechanistic studies to support these observations. We therefore obtained early/mid-gestation and term placentae from 20 HIV/Hepatitis B/CMV negative women.

Maternal T Cells in the Human Placental Villi Support an Allograft Response during Noninfectious Villitis.

During human pregnancy, proinflammatory responses in the placenta can cause severe fetal complications, including growth restriction, preterm birth, and stillbirth. Villitis of unknown etiology (VUE), an inflammatory condition characterized by the infiltration of maternal CD8 T cells into the placenta, is hypothesized to be secondary to either a tissue rejection response to the haploidentical fetus or from an undiagnosed infection. In this study, we characterized the global TCR β-chain profile in human T cells isolated from placentae diagnosed with VUE compared with control and infectious villitis-placentae by immunoSEQ.

Baby's First Macrophage: Temporal Regulation of Hofbauer Cell Phenotype Influences Ligand-Mediated Innate Immune Responses across Gestation.

The importance of fetal placental macrophages (Hofbauer cell [HCs]) is underscored by their appearance 18 d postconception and maintenance through term; however, how human HCs evolve during healthy pregnancy and how microenvironment and ontogeny impact phenotype and function remain unknown. In this study, we comprehensively classify human HCs ex vivo, interrogate phenotypic plasticity, and characterize antiviral immune responses through gestation. Activated HCs were abundant in early pregnancy and decreased by term; molecular signatures emphasize inflammatory phenotypes early in gestation.

Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages.

Zika virus (ZIKV), which emerged in regions endemic to dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission remains unclear. Here, we find that DENV antibodies increase ZIKV infection of placental macrophages (Hofbauer cells [HCs]) from 10% to over 80% and enhance infection of human placental explants.

Human Cytomegalovirus Enhances Placental Susceptibility and Replication of Human Immunodeficiency Virus Type 1 (HIV-1), Which May Facilitate In Utero HIV-1 Transmission.

Several co-pathogens that pose threats to the fetus during gestation, including human cytomegalovirus (HCMV), may also contribute to mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1). Within endemic settings, associations between maternal HCMV viral load and increased incidence of MTCT of HIV-1 are documented; however, the mechanisms that promote transmission are poorly characterized. Here we demonstrate that HCMV coinfection enhances susceptibility and viral replication of HIV-1 in placental macrophages (Hofbauer cells) in vitro.

Jak Inhibitors Modulate Production of Replication-Competent Zika Virus in Human Hofbauer, Trophoblasts, and Neuroblastoma cells.

Zika Virus (ZIKV) is a flavivirus that has been implicated in causing brain deformations, birth defects, and microcephaly in fetuses, and associated with Guillain-Barre syndrome. Mechanisms responsible for transmission of ZIKV across the placenta to the fetus are incompletely understood. Herein, we define key events modulating infection in clinically relevant cells, including primary placental macrophages (human Hofbauer cells; HC), trophoblasts, and neuroblastoma cells.

Zika Virus Infects Human Placental Macrophages.

The recent Zika virus (ZIKV) outbreak in Brazil has been directly linked to increased cases of microcephaly in newborns. Current evidence indicates that ZIKV is transmitted vertically from mother to fetus. However, the mechanism of intrauterine transmission and the cell types involved remain unknown.

HIV-1 at the placenta: immune correlates of protection and infection.

Purpose Of Review: Mother-to-child transmission (MTCT) of HIV-1 remains a significant global health concern despite implementation of maternal combination antiretroviral therapy for treatment as prevention to offset transmission. The risk of in-utero HIV-1 transmission in the absence of interventions is ∼7%. This low rate of transmission points to innate and adaptive mechanisms to restrict lentiviral infection within the placenta.

Placental Hofbauer cells assemble and sequester HIV-1 in tetraspanin-positive compartments that are accessible to broadly neutralizing antibodies.

Introduction: Within monocyte-derived macrophages, HIV-1 accumulates in intracellular virus-containing compartments (VCCs) that are inaccessible to the external environment, which implicate these cells as latently infected HIV-1 reservoirs. During mother-to-child transmission of HIV-1, human placental macrophages (Hofbauer cells (HCs)) are viral targets, and have been shown to be infected in vivo and sustain low levels of viral replication in vitro; however, the risk of in utero transmission is less than 7%. The role of these primary macrophages as viral reservoirs is largely undefined.

Cytomegalovirus upregulates expression of CCR5 in central memory cord blood mononuclear cells, which may facilitate in utero HIV type 1 transmission.

Administration of combination antiretroviral therapy to human immunodeficiency virus type 1 (HIV-1)-infected pregnant women significantly reduces vertical transmission. In contrast, maternal co-opportunistic infection with primary or reactivated cytomegalovirus (CMV) or other pathogens may facilitate in utero transmission of HIV-1 by activation of cord blood mononuclear cells (CBMCs). Here we examine the targets and mechanisms that affect fetal susceptibility to HIV-1 in utero.

Differences in caregiver self-efficacy and satisfaction related to sexual abuse of offspring.

Research suggests parents of sexually abused children may experience negative perceptions of themselves and their parenting abilities following the victimization of their children, which may influence the recovery process in treatment for these families. This study assessed perceived self-efficacy and parenting satisfaction among female caregivers of sexually abused children and female caregivers whose children were not victimized. Results indicated that caregivers of child victims had significantly lower levels of perceived parenting efficacy than their counterparts.

Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines.

Background: Despite readily detectable levels of the HIV-1 (co)-receptors CD4, CCR5 and DC-SIGN on placental macrophages (Hofbauer Cells [HCs]), the rate of HIV-1 infection in utero in the absence of interventions is only 7% of exposed infants. Here, we examine the replication kinetics of human HCs to the primary isolate HIV-1BaL. We also determined the infectivity of HIV-1-exposed HCs by co-culturing with isolated cord and peripheral blood mononuclear cells [CBMCs, PBMCs].

CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion.

Background: Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa) cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites.

CCL25-CCR9 interaction modulates ovarian cancer cell migration, metalloproteinase expression, and invasion.

Background: Ovarian carcinoma (OvCa) is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells and its only natural ligand, CCL25, is largely expressed in the thymus, which involutes with age. Other than the thymus, CCL25 is expressed by the small bowel.

CCR9 interactions support ovarian cancer cell survival and resistance to cisplatin-induced apoptosis in a PI3K-dependent and FAK-independent fashion.

Background: Cisplatin is more often used to treat ovarian cancer (OvCa), which provides modest survival advantage primarily due to chemo-resistance and up regulated anti-apoptotic machineries in OvCa cells. Therefore, targeting the mechanisms responsible for cisplatin resistance in OvCa cell may improve therapeutic outcomes. We have shown that ovarian cancer cells express CC chemokine receptor-9 (CCR9).