Interferon lambda signals in maternal tissues to exert protective and pathologic effects in a gestational-stage dependent manner

Interferon lambda (IFN-λ, type III IFN) is constitutively secreted from human placental cells in culture and reduces Zika virus (ZIKV) transplacental transmission in mice. However, the roles of IFN-λ during healthy pregnancy and in restricting congenital infection remain unclear. Here we used mice lacking the IFN-λ receptor (Ifnlr1-/-) to generate pregnancies lacking either maternal or fetal IFN-λ responsiveness and found that the antiviral effect of IFN-λ resulted from signaling exclusively in maternal tissues. This protective effect depended on gestational stage, as infection earlier in pregnancy (E7 rather than E9) resulted in enhanced transplacental transmission of ZIKV. In Ifnar1-/- dams, which sustain robust ZIKV infection, maternal IFN-λ signaling caused fetal resorption and intrauterine growth restriction. Pregnancy pathology elicited by poly(I:C) treatment also was mediated by maternal IFN-λ signaling, specifically in maternal leukocytes, and also occurred in a gestational stage-dependent manner. These findings identify an unexpected effect of IFN-λ signaling specifically in maternal (rather than placental or fetal) tissues, which is distinct from the pathogenic effects of IFN-αβ (type I IFN) during pregnancy. These results highlight the complexity of immune signaling at the maternal-fetal interface, where disparate outcomes can result from signaling at different gestational stages.

Overwhelming Evidence Transplacental Transmission of Human Papillomavirus Primarily Causes Autism

Because the concordance rate between identical twins is only 88%, an environmental factor must cause autism spectrum disorder (ASD). Furthermore, when identical twins share ASD, it is to varying degrees suggesting different prenatal environments exist, which occurs when identical twins have separate placentas (~30% of the time). Placental inclusions are predictive of ASD along with excessive increases in extra-axial cerebral spinal fluid (CSF) detected by MRI in the brains of 6- and 12-month-old infants later diagnosed at 2 years with ASD. The human papillomavirus (HPV) can infect the trophoblast cells of placentas and transmit to the fetus where it infects the epithelial cells of the choroid plexus, a centrally located lining inside the brain responsible for producing CSF via the SLC4A10 gene product. HPV causes epigenetic changes, deletions, and duplications of genes, and besides its characteristic methylation patterns, the SLC4A10 gene was found to be increased in children with ASD. Moreover, male placentas implant close to the cervix (low-lying) three times more often than female placentas paralleling the ASD ratio of ~3:1 (boys to girls). Finally, the Australian HPV vaccination programme that began in 2007 might explain why the 0-4 yr. ASD incidence did not increase from 2010 to 2015.

Is It Possible to Intervene in the Capacity of Trypanosoma cruzi to Elicit and Evade the Complement System?

Chagas’ disease is a zoonotic parasitic ailment now affecting more than 6 million people, mainly in Latin America. Its agent, the protozoan Trypanosoma cruzi, is primarily transmitted by endemic hematophagous triatomine insects. Transplacental transmission is also important and a main source for the emerging global expansion of this disease. In the host, the parasite undergoes intra (amastigotes) and extracellular infective (trypomastigotes) stages, both eliciting complex immune responses that, in about 70% of the cases, culminate in permanent immunity, concomitant with the asymptomatic presence of the parasite. The remaining 30% of those infected individuals will develop a syndrome, with variable pathological effects on the circulatory, nervous, and digestive systems. Herein, we review an important number of T. cruzi molecules, mainly located on its surface, that have been characterized as immunogenic and protective in various experimental setups. We also discuss a variety of parasite strategies to evade the complement system - mediated immune responses. Within this context, we also discuss the capacity of the T. cruzi infective trypomastigote to translocate the ER-resident chaperone calreticulin to its surface as a key evasive strategy. Herein, it is described that T. cruzi calreticulin inhibits the initial stages of activation of the host complement system, with obvious benefits for the parasite. Finally, we speculate on the possibility to experimentally intervene in the interaction of calreticulin and other T. cruzi molecules that interact with the complement system; thus resulting in significant inhibition of T. cruzi infectivity.

Literature Review: Transplacental Transmission of COVID-19 and Its Teratological Aspect

Coronavirus disease 2019 (Covid-19) pandemic affects all populations, including pregnant women. Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in pregnancy needs to be a concern because of the risk of transplacental transmission to the fetus and the potential to interfere with fetal development. The objective of this study is to review the transplacental transmission of COVID-19 and the teratological aspects of the event. This article is a literature study. Based on the literature obtained, placental infection, vertical transmission, and fetal infection have been identified in some cases. However, there is still no consistent and enough scientific evidence to show that those condition causes fetal damage or causes congenital anomalies. Virus and host characteristics are thought to explain why SARS-Cov-2 infection has not shown a teratological effect. SARS-CoV-2, similar to severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) infection, does not indicate maternal-fetal transmission. The low-level expression of angiotensin-converting enzyme 2 (ACE2) and S protein priming proteases type II transmembrane serine protease (TMPRSS 2) in the placenta is also considered to be the factor that plays a role in inhibiting the vertical transmission of COVID-19. Adverse outcome of fetal death is more due to pathophysiological conditions of maternal health caused by SARS-CoV-2 infection during gestation.

The Effects of COVID-19 on the Placenta During Pregnancy

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.

Defining Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Placentitis: A Report of 7 Cases with Confirmatory In Situ Hybridization, Distinct Histomorphologic Features, and Evidence of Complement Deposition

Context.–Case reports and rare case series have demonstrated variable placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In rare small studies demonstrating infection of the placental parenchyma, histologic manifestations have included variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and syncytiotrophoblast necrosis. Objective.–To characterize the placental pathological features of SARS-CoV-2 infected placentas, irrespective of fetal-maternal transmission, and to examine the frequency of C4d activation in such cases. Design.–Retrospective study of seven placentas from mothers with active SARS-CoV-2 infection and placental infection as demonstrated by RNA in situ hybridization. Results.–Six placentas were from live-born neonates (5 singletons, 1 non-fused diamniotic-dichorionic twin placenta), and one was from a stillbirth. Five of the eight neonates (including the stillbirth) tested negative for SARS-CoV-2, and all were negative for neonatal infection. The remaining three neonates were well at time of discharge. All placentas were positive for SARS-CoV-2 infection by RNA in situ hybridization and demonstrated variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. Three cases demonstrated features of fetal vascular malperfusion. CD68 highlighted intervillous histiocytes. C4d expression was present along the villous borders in 6 of 7 cases. Conclusions.–SARS-CoV-2 placentitis is defined by the triad of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. The features may occur in cases without confirmed transplacental transmission. The damage caused by SARS-CoV-2 placentitis is likely mediated by complement activation.

Impact of joint management of a COVID-19 mother and her newborn on the virus transmission: a case report

Background Since last year, COVID-19, the disease caused by the novel Sars-Cov-2 virus, has been globally spread to all the world. COVID-19 infection among pregnant women has been described. However, transplacental transmission of Sars-Cov-2 virus from infected mother to the newborn is not yet established. The appropriate management of infants born to mothers with confirmed or suspected COVID-19 and the start of early breastfeeding are being debated. Case presentation We report a case of the joint management of a healthy neonate with his mother tested positive for Covid-19 before the delivery and throughout neonatal follow-up. The infection transmission from the mother to her baby is not described, even after a long period of contact between them and breastfeeding. Conclusion It may consider an appropriate practice to keep mother and her newborn infant together in order to facilitate their contact and to encourage breastfeeding, although integration with infection prevention measures is needed.

Pregnant with COVID-19 and Rubella: Impact in the Maternal and Newborn Health

Since December 2019, COVID-19 has become major global public health problem. The understanding of SARS-CoV-2, especially the effect on pregnant women and neonates, is still not fully elucidated. This report case describes a pregnant with COVID-19 and rubella. SARS-CoV-2 nucleic acid was not detected in the neonate just after birth, indicating that there was not vertical transmission. Although anti-SARS-CoV-2 Immunoglobulin G (IgG) antibody and anti-Rubella Virus IgG antibody were detected in the newborn serum, anti-SARS-CoV-2 (Immunoglobulin M) IgM and anti-Rubella Virus IgM were not detected. The observations may suggest transplacental transmission of coronavirus and rubella antibodies, ensuring immediate immunity against these pathogens to newborn.