A microscopical study of wound repair in the human placenta

Romero

The Journal of Immunology

et al. 2009

176

175

The co-presence of histoincompatible fetal and maternal cells is a characteristic of human placental inflammation. Villitis of unknown etiology (VUE), a destructive inflammatory lesion of villous placenta, is characterized by participation of Hofbauer cells (placental macrophages) and maternal T cells. In contrast to acute chorioamnionitis of infection-related origin, the fundamental immunopathology of VUE is unknown. This study was performed to investigate the placental transcriptome of VUE and to determine whether VUE is associated with systemic maternal and/or fetal inflammatory response(s). Comparison of the transcriptome between term placentas without and with VUE revealed differential expression of 206 genes associated with pathways related to immune response. The mRNA expression of a subset of chemokines and their receptors (CXCL9, CXCL10, CXCL11, CXCL13, CCL4, CCL5, CXCR3, CCR5) was higher in VUE placentas than in normal placentas (p < 0.05). Analysis of blood cell mRNA showed a higher expression of CXCL9 and CXCL13 in the mother, and CXCL11 and CXCL13 in the fetus of VUE cases (p < 0.05). The median concentrations of CXCL9, CXCL10, and CXCL11 in maternal and fetal plasma were higher in VUE (p < 0.05). Comparison of preterm cases without and with acute chorioamnionitis revealed elevated CXCL9, CXCL10, CXCL11, and CXCL13 concentrations in fetal plasma (p < 0.05), but not in maternal plasma with chorioamnionitis. We report for the first time the placental transcriptome of VUE. A systemic derangement of CXC chemokines in maternal and fetal circulation distinguishes VUE from acute chorioamnionitis. We propose that VUE be a unique state combining maternal allograft rejection and maternal antifetal graft-vs-host disease mechanisms.

Section: Discussionmentioning

confidence: 99%

Villitis of Unknown Etiology Is Associated with a Distinct Pattern of Chemokine Up-Regulation in the Feto-Maternal and Placental Compartments: Implications for Conjoint Maternal Allograft Rejection and Maternal Anti-Fetal Graft-versus-Host Disease

Romero

The Journal of Immunology

et al. 2009

176

175

“…The demonstration that HBC cluster at sites of fibrinoid necrosis in vivo ( 12 ) and also to sites of villous damage in vitro ( 34 ), indicates that the migratory capacity of first trimester HBC is important for placental function, repair and defense. TGFβ1 was found to be highly expressed at sites of tissue injury and recruited HBC, suggesting it is involved in the placental wound repair process ( 34 ).…”

Section: Hbcmentioning

confidence: 99%

The Ontogeny and Function of Placental Macrophages

et al. 2021

The placenta is a fetal-derived organ whose function is crucial for both maternal and fetal health. The human placenta contains a population of fetal macrophages termed Hofbauer cells. These macrophages play diverse roles, aiding in placental development, function and defence. The outer layer of the human placenta is formed by syncytiotrophoblast cells, that fuse to form the syncytium. Adhered to the syncytium at sites of damage, on the maternal side of the placenta, is a population of macrophages termed placenta associated maternal macrophages (PAMM1a). Here we discuss recent developments that have led to renewed insight into our understanding of the ontogeny, phenotype and function of placental macrophages. Finally, we discuss how the application of new technologies within placental research are helping us to further understand these cells.

“…Future studies by electron microscopy to determine if progeny virus is sequestered in vacuoles in the trophoblast as in macrophages [14] or released and trapped in the electron-dense layer are therefore warranted. Burton and Watson (6) suggest that the basement membrane is an important placental barrier, since transient trophoblast damage down to the TBM followed by repair is often observed without concomitant fetal consequences (5,54). Lack of basal release from infected trophoblasts and/or the presence of a TBM acting as an effective barrier may explain why vertical transmission does not occur more frequently in the first trimester than in the third trimester (9,29) even though first-trimester trophoblasts are more readily infected (22).…”

mentioning

confidence: 99%

Polarized Release of Human Cytomegalovirus from Placental Trophoblasts

Hemmings

Guilbert

2002

J Virol

Human cytomegalovirus (HCMV) is a ubiquitous infectious pathogen that, when transmitted to the fetus in utero, can result in numerous sequelae, including late-onset sensorineural damage. The villous trophoblast, the cellular barrier between maternal blood and fetal tissue in the human placenta, is infected by HCMV in vivo. Primary trophoblasts cultured on impermeable surfaces can be infected by HCMV, but release of progeny virus is delayed and minimal. It is not known whether these epithelial cells when fully polarized can release HCMV and, if so, if release is from the basal membrane surface toward the fetus. We therefore ask whether, and in which direction, progeny virus release occurs from HCMV-infected trophoblasts cultured on semipermeable (3.0-m-pore-size) membranes that allow functional polarization. We show that infectious HCMV readily diffuses across cell-free 3.0-m-pore-size membranes and that apical infection of confluent and multilayered trophoblasts cultured on these membranes reaches cells at the membrane surface. Using two different infection and culture protocols, we found that up to 20% of progeny virus is released but that <1% of released virus is detected in the basal culture chamber. These results suggest that very little, if any, HCMV is released from an infected villous trophoblast into the villous stroma where the virus could ultimately infect the fetus.Human cytomegalovirus (HCMV) is endemic, infecting 40 to 80% of urban populations in developed countries (10). The incidence of congenital HCMV infection is between 0.2 and 2.2% of all live-born infants. Such infections are one of the most common causes of mental retardation and nonhereditary sensorineural deafness in children (46,48). Only 40% of pregnant women with primary HCMV infections give birth to infected infants (47) suggesting an effective fetal barrier, either physical or immunological. How HCMV is transmitted to the fetus during pregnancy is unknown; however, congenital infections are associated with chronic villitis (38, 41) and infection of the placenta (1, 4, 16, 32, 36-39, 41, 44, 45), which may also act as a viral reservoir (19). Passage through the placenta (2, 3) could occur in two directions: through the cytotrophoblast (CT) columns in anchoring villi or across the villous syncytiotrophoblast (ST) in the intervillous space.Infection originating in the uterine wall could lead to infection of extravillous CT involved in either interstitial or endovascular invasion. Infection could then progress in a cell-to-cell manner through the CT columns of anchoring villi to the chorionic stroma and eventually infect the fetus (15). Although this route is possible during a reactivated uterine infection, endovascular CT comes into direct contact with maternal blood and therefore could also be exposed to a primary infection.The ST lines all chorionic villi within the intervillous space, thereby interfacing maternal blood and fetal tissues. The ST is thus positioned to either physically prevent or to actively participate in the dissemina...