Teratogenic parasites: disease mechanisms and emerging study models.

Congenital infections are a leading preventable cause of pregnancy complications impacting both mother and fetus. Although advancements have been made in understanding various congenital infections, the mechanisms of parasitic infections during pregnancy remain poorly understood. This review covers the global incidence of three parasites capable of congenital transmission - Trypanosoma cruzi, Plasmodium spp.

infection misdirects placental trophoblast lineage specification.

Pregnancy is a critical point of vulnerability to infection and other insults that could compromise proper fetal development. The placenta acts as a protective and nutrient-permeable barrier to most infectious agents, but a few are capable of bypassing its defenses. Remarkably little is known about how exposure to these select pathogens might impact ongoing placental development.

The trophoblast surface becomes refractory to adhesion by congenitally transmitted and during cytotrophoblast to syncytiotrophoblast development.

The placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance of understanding these mechanisms and challenges in replicating trophoblast-pathogen interactions using models, we tested an existing stem-cell-derived model of trophoblast development for its relevance to infection with .

Systematic Review and Meta-Analysis of Congenital Toxoplasmosis Diagnosis: Advances and Challenges.

Objective: To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis.

Methods: PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: "congenital toxoplasmosis" or "gestational toxoplasmosis" and "diagnosis" and "blood," "serum," "amniotic fluid," "placenta," or "colostrum.

P21 recombinant protein modulates infection in different experimental models of the human maternal-fetal interface.

Introduction: is the etiologic agent of toxoplasmosis, a disease that affects about one-third of the human population. Most infected individuals are asymptomatic, but severe cases can occur such as in congenital transmission, which can be aggravated in individuals infected with other pathogens, such as HIV-positive pregnant women. However, it is unknown whether infection by other pathogens, such as , the etiologic agent of Chagas disease, as well as one of its proteins, P21, could aggravate infection.

Polyalthic acid and oleoresin from Copaifera trapezifolia Hayne reduce Toxoplasma gondii growth in human villous explants, even triggering an anti-inflammatory profile.

Due to the lack of efficient antiparasitic therapy and vaccines, as well as emerging resistance strains, congenital toxoplasmosis is still a public health issue worldwide. The present study aimed to assess the effects of an oleoresin obtained from the species Copaifera trapezifolia Hayne (CTO), and an isolated molecule found in the CTO, ent-polyalthic acid (ent-15,16-epoxy-8(17),13(16),14-labdatrien-19-oic acid) (named as PA), against T. gondii infection.

Macrophage Migration Inhibitory Factor contributes to drive phenotypic and functional macrophages activation in response to Toxoplasma gondii infection.

Cytokines are small molecules secreted by numerous cells. Macrophage Migration Inhibitory Factor (MIF) is a cytokine initially described due to its function of inhibiting random macrophage migration. Currently, new functions have been described for MIF, such as stimulating inflammatory functions in response to infections by microorganisms including, Toxoplasma gondii.

LPS-mediated activation of TLR4 controls Toxoplasma gondii growth in human trophoblast cell (BeWo) and human villous explants in a dependent-manner of TRIF, MyD88, NF-κB and cytokines.

We evaluated the influence of the Toll-like receptor (TLR)-4 pathways on BeWo, JEG-3 and HTR-8/SVneo cells, as well as in human villous explants infected with Toxoplasma gondii. Cells and explants were stimulated with LPS for 24 or 48 h and processed for the MTT assay, and expression of TLR4 was evaluated by confocal microscopy. In addition, we used peptides that inhibit MyD88 or TRIF, and inhibitor to NF-κB.

Transforming growth factor (TGF)-β1 and interferon (IFN)-γ differentially regulate ICAM-1 expression and adhesion of Toxoplasma gondii to human trophoblast (BeWo) and uterine cervical (HeLa) cells.

Toxoplasma gondii is a parasite able to infect various cell types, including trophoblast cells. Studies have demonstrated that interleukin (IL)-10, transforming growth factor (TGF)-β1 and interferon (IFN)-γ are involved in the susceptibility of BeWo trophoblast cells to T. gondii infection.

Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants.

Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. Our studies demonstrated that T. gondii developed mechanisms to evade of the host immune response, such as cyclooxygenase (COX)-2 and prostaglandin E (PGE) induction, and these mediators can be produced/stored in lipid droplets (LDs).

ERK1/2 phosphorylation and IL-6 production are involved in the differential susceptibility to Toxoplasma gondii infection in three types of human (cyto/ syncytio/ extravillous) trophoblast cells.

During pregnancy, Toxoplasma gondii can triggers serious manifestations and potentially affect the fetal development. In this scenario, differences in susceptibility of trophoblast cells to T. gondii infection might be evaluated in order to establish new therapeutic approaches capable of interfering in the control of fetal infection by T.

Predicted impacts of government policies and actions on the SARS-CoV-2 disease in the northwestern Himalayan region, India.

Aim: The outbreak of the new coronavirus pandemic (SARS-CoV-2) was initiated in December 2019, and within a couple of months it became a global health emergency. Given the importance to assess the evolution and transmissibility of SARS-CoV-2 and to forecast the next scenario of the pandemic, mainly in countries with limited healthcare systems, we estimated the reproductive number (R0) of SARS-CoV-2 in Jammu and Kashmir (J&K), India, and a possible scenario for this pandemic in the region.

Subject And Methods: We estimated the reproductive number (R0) of SARS-CoV-2 in its first outbreak stage in the northwestern region of Himalaya, India, and we also predicted new daily cases for the next 90 days using different R0, testing a plausible end of the SARS-CoV-2 outbreak.

Erratum to "Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by infection" [Cytokine: X 2 (2020) 100034].

[This corrects the article DOI: 10.1016/j.cytox.

Biogenic Silver Nanoparticles Can Control Infection in Both Human Trophoblast Cells and Villous Explants.

The combination of sulfadiazine and pyrimethamine plus folinic acid is the conventional treatment for congenital toxoplasmosis. However, this classical treatment presents teratogenic effects and bone marrow suppression. In this sense, new therapeutic strategies are necessary to reduce these effects and improve the control of infection.

Experimental models of maternal-fetal interface and their potential use for nanotechnology applications.

During pregnancy, the placenta regulates the transfer of oxygen, nutrients, and residual products between the maternal and fetal bloodstreams and is a key determinant of fetal exposure to xenobiotics from the mother. To study the disposition of substances through the placenta, various experimental models are used, especially the perfused placenta, placental villi explants, and cell lineage models. In this context, nanotechnology, an area of study that is on the rise, enables the creation of particles on nanometric scales capable of releasing drugs aimed at specific tissues.

Increased Intracellular Proliferation in Human Extravillous Trophoblast Cells (HTR8/SVneo Line) Is Sequentially Triggered by MIF, ERK1/2, and COX-2.

Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine, which mediates the regulation of diverse cellular functions. It is produced by extravillous trophoblastic cells and has been found to be involved in the pathogenesis of diseases caused by some protozoa, including . Previous studies demonstrated the ability of to take advantage of MIF action in human trophoblast cells.

Cyclooxygenase (COX)-2 Inhibitors Reduce Infection and Upregulate the Pro-inflammatory Immune Response in Rodents and Human Monocyte Cell Line.

is able to infect a wide range of vertebrates, including humans. Studies show that cyclooxygenase-2 (COX-2) is a modulator of immune response in multiple types of infection, such as . However, the role of COX-2 during infection is still unclear.

Brazilian strains of Toxoplasma gondii are controlled by azithromycin and modulate cytokine production in human placental explants.

Background: Toxoplasma gondii is a protozoan parasite that causes congenital toxoplasmosis by transplacental transmission. Parasite strains are genetically diverse and disease severity is related to the genotype. In Uberlândia city, Brazil, two virulent strains were isolated: TgChBrUD1 and TgChBrUD2.

Macrophage Migration Inhibitory Factor (MIF) Prevents Maternal Death, but Contributes to Poor Fetal Outcome During Congenital Toxoplasmosis.

Migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays important roles in physiology, pathology, immunology and parasitology, including the control of infection by protozoa parasites such as . As the MIF function in congenital toxoplasmosis is not fully elucidated yet, the present study brings new insights for infection in the absence of MIF based on pregnant C57BL/6MIF mouse models. Pregnant C57BL/6MIF and C57BL/6WT mice were infected with 05 cysts of (ME49 strain) on the first day of pregnancy (dop) and were euthanized at 8 dop.

Antiparasitic effects induced by polyclonal IgY antibodies anti-phospholipase A from Bothrops pauloensis venom.

Activities of phospholipases (PLAs) have been linked to pathogenesis in various microorganisms, and implicated in cell invasion and so the interest in these enzymes as potential targets that could contribute to the control of parasite survival and proliferation. Chicken eggs immunized with BnSP-7, a Lys49 phospholipase A (PLA) homologue from Bothrops pauloensis snake venom, represent an excellent source of polyclonal antibodies with potential inhibitory activity on parasite PLA Herein, we report the production, characterization and anti-parasitic effect of IgY antibodies from egg yolks of hens immunized with BnSP-7. Produced antibodies presented increasing avidity and affinity for antigenic toxin epitopes throughout immunization, attaining a plateau after 4weeks.

Azithromycin treatment is able to control the infection by two genotypes of Toxoplasma gondii in human trophoblast BeWo cells.

Trophoblast infection by Toxoplasma gondii plays a pivotal role in the vertical transmission of toxoplasmosis. Here, we investigate whether the antibiotic therapy with azithromycin, spiramycin and sulfadiazine/pyrimethamine are effective to control trophoblast infection by two Brazilian T. gondii genotypes, TgChBrUD1 or TgChBrUD2.

Enrofloxacin and Toltrazuril Are Able to Reduce Growth in Human BeWo Trophoblastic Cells and Villous Explants from Human Third Trimester Pregnancy.

Classical treatment for congenital toxoplasmosis is based on combination of sulfadiazine and pyrimethamine plus folinic acid. Due to teratogenic effects and bone marrow suppression caused by pyrimethamine, the establishment of new therapeutic strategies is indispensable to minimize the side effects and improve the control of infection. Previous studies demonstrated that enrofloxacin and toltrazuril reduced the incidence of and infection.