Congenital Transmission of Trypanosoma cruzi: A Review About the Interactions Between the Parasite, the Placenta, the Maternal and the Fetal/Neonatal Immune Responses

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, is considered a neglected tropical disease by the World Health Organization. Congenital transmission of CD is an increasingly relevant public health problem. It progressively becomes the main transmission route over others and can occur in both endemic and non-endemic countries. Though most congenitally infected newborns are asymptomatic at birth, they display higher frequencies of prematurity, low birth weight, and lower Apgar scores compared to uninfected ones, and some suffer from severe symptoms. If not diagnosed and treated, infected newborns are at risk of developing disabling and life-threatening chronic pathologies later in life. The success or failure of congenital transmission depends on interactions between the parasite, the placenta, the mother, and the fetus. We review and discuss here the current knowledge about these parameters, including parasite virulence factors such as exovesicles, placental tropism, potential placental defense mechanisms, the placental transcriptome of infected women, gene polymorphism, and the maternal and fetal/neonatal immune responses, that might modulate the risk of T. cruzi congenital transmission.This work was supported by the ERANET-LAC grants ELAC2014/HID-0328 and ERANet17/HLH-0142 (to UK, AO, AS, and CT), FONDECYT 1190341 (Conicyt, Chile to UK), and PICT 2015-0074 (FONCyT, Argentina to AS)

Lipoteichoic acid stimulates the proliferation, migration and cytokine production of adult dental pulp stem cells without affecting osteogenic differentiation

Aim: To model in vitro the contact between adult dental pulp stem cells (DPSCs) and lipoteichoic acid (LTA), a cell wall component expressed at the surface of most Gram-positive bacteria. Methodology: Human DPSCs obtained from impacted third molars were cultured and exposed to various concentrations of S. aureus LTA (0.1, 1.0 and 10 µg mL −1). The effects of LTA on DPSCs proliferation and apoptosis were investigated by MTT assay and flow cytometry. Mineralization of DPSCs was evaluated by alizarin red staining assay. Migration was investigated by microphotographs of wound-healing and Transwell migration assays. Reverse transcription polymerase chain reaction was used to examine the effects of LTA on p65 NF-κB translocation and TLR1, TLR2 or TLR6 regulation. Enzyme-linked immunosorbent assay was used to investigate LTA-stimulated DPSCs cytokine production. One-way or two-way ANOVA and Tukey post hoc multiple comparison were used for statistical analysis. Results: DPSCs expressed TLR1, TLR2 and TLR6 involved in the recognition of various forms of LTA or lipoproteins. Exposure to LTA did not up- or down-regulate the mRNAs of TLR1, TLR2 or TLR6 whilst LPS acted as a potent inducer of them [TLR1 (P ≤ 0.05), TLR2 (P ≤ 0.001) and TLR6 (P ≤ 0.001)]. Translocation of p65 NF-κB to the nucleus was detected in LTA-stimulated cells, but to a lesser extent than LPS-stimulated DPSCs (P ≤ 0.001). The viability of cells exposed to LTA was greater than unstimulated cells, which was attributed to an increased proliferation and not to less cell death [LTA 1 μg mL −1 (P ≤ 0.001) and 10 μg mL −1 (P ≤ 0.01)]. For specific doses of LTA (1.0 µg mL −1), adhesion of DPSCs to collagen matrix was disturbed (P ≤ 0.05) and cells enhanced their horizontal mobility (P ≤ 0.001). LTA-stimulated DPSCs released IL-6 and IL-8 in a dose-dependent manner (P ≤ 0.0001). At all concentrations investigated, LTA did not influence osteogenic/odontoblastic differentiation. Conclusions: Human DPSCs were able to sense the wall components of Gram-positive bacteria likely through TLR2 signalling. Consequently, cells modestly proliferated, increased their migratory behaviour and contributed significantly to the local inflammatory response through cytokine release. </p

Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection

Chagas disease is a neglected disease caused by Trypanosoma cruzi parasites. Most diagnosis is based on serological tests, but the lack of a gold standard test complicates the measurement of test performance. To overcome this limitation, we used samples from a cohort of well-characterized T. cruzi-infected women to evaluate the reactivity of two rapid diagnostic tests and one enzyme-linked immunosorbent assay (ELISA). Our cohort was derived from a previous study on congenital transmission of T. cruzi and consisted of 481 blood/plasma samples from Argentina (n = 149), Honduras (n = 228), and Mexico (n = 104), with at least one positive T. cruzi PCR. Reactivity of the three tests ranged from 70.5% for the Wiener ELISA to 81.0% for the T-Detect and 90.4% for the Stat-Pak rapid tests. Test reactivity varied significantly among countries and was highest in Argentina and lowest in Mexico. When considering at least two reactive serological tests to confirm seropositivity, over 12% of T. cruzi infection cases from Argentina were missed by serological tests, over 21% in Honduras, and an alarming 72% in Mexico. Differences in test performance among countries were not due to differences in parasitemia, but differences in antibody levels against ELISA antigens were observed. Geographic differences in T. cruzi parasite strains as well as genetic differences among human populations both may contribute to the discrepancies in serological testing. Improvements in serological diagnostics for T. cruzi infections are critically needed to ensure an optimum identification of cases.Fil: Truyens, Carine. Université Libre de Bruxelles; BélgicaFil: Dumonteil, Eric. University of Tulane; Estados UnidosFil: Alger, Jackeline. Universidad Nacional Autónoma de Honduras; HondurasFil: Cafferata, Maria Luisa. No especifíca;Fil: Ciganda, Alvaro. No especifíca;Fil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Herrera, Claudia. University of Tulane; Estados UnidosFil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Buekens, Pierre. University of Tulane; Estados Unido

Evaluation of a commercial IgG monotest assay: a new automated chemiluminescent immunoassay for the serodiagnosis of cystic echinococcosis

Background: Cystic echinococcosis (CE) is a zoonotic disease caused by the tapeworm Echinococcus granulosus complex. The geographical distribution is worldwide with variable incidences. In Belgium, only few imported cases are reported each year. Serodiagnosis of CE is performed by using a combination of immunoassays which are mainly based on crude hydatid antigens. The Belgian National Reference Laboratory, has evaluated the CE-IVD Hydatidosis VirClia® IgG chemiluminescent immunoassay and compared it with two other immunoassays. Methods: A total of 79 sera were retrospectively included from 15 patients with CE, 29 with alveolar echinococcosis, 16 with toxocariasis and 19 negative controls. Three immunoassays were compared: the Hydatidosis VirClia® IgG monotest assay which was run on the Virclia® Lotus (Vircell, Spain); the Ridascreen® Echinococcus IgG assay (R-Biopharm, Germany) and the Bordier® Echinococcus granulosus IgG ELISA (Bordier, Switzerland), which were tested on the ETI-Max 3000 immunoassay analyzer (DiaSorin, Italy). The McNemar test is used for statistical analysis. Results: All three methods showed 100% sensitivity. Regarding specificity, the Ridascreen® (78.1%) and VirClia® (76.6%) assays showed comparable performance (p-value: 1), while the Bordier® assay had poor results (54,7%) (p-value: 0,0007). The Bordier® assay showed 76% cross-reactions with E. multilocularis (22/29) and 31% with Toxocara sp. (5/16), while the VirClia® assay showed 51,7% (15/29) and no cross-reaction with Toxocara antigens. For Ridascreen® assay, 34% and 19% cross-reactions were observed for E. multilocularis (10/29) and Toxocara sp. (3/16), respectively. Non-specific reactions in negative controls were only observed with the Ridascreen® (1/19) and Bordier® assays (2/19). The shortest turnaround time was observed with Virclia® Lotus: 1 hour versus 3 hours for two other assays. Conclusions: All assays showed very high sensitivity. However, regarding specificity, the VirClia® performs better than the Bordier® and similarly to the Ridascreen® assay. Besides, the ready-to-use monotest format offers many advantages such as a quicker methodology and a reduced workflow. Therefore, the VirClia® assay is an efficient screening method for the detection of CE but should always be combined with an immunoblot assay to assess the specificity

Genetic diversity of Echinococcus multilocularis specimens isolated from Belgian patients with alveolar echinococcosis using EmsB microsatellites analysis.

The genetic diversity of Echinococcus multilocularis (E. multilocularis) specimens isolated from patients with alveolar echinococcosis (AE), is a major field of investigation to correlate with sources of infection, clinical manifestations and prognosis of the disease. Molecular markers able to distinguish samples are commonly used worldwide, including the EmsB microsatellite. Here, we report the use of the EmsB microsatellite polymorphism data mining for the retrospective typing of Belgian specimens of E. multilocularis infecting humans. A total of 18 samples from 16 AE patients treated between 2006 and 2021 were analyzed through the EmsB polymorphism. Classification of specimens was performed through a dendrogram construction in order to compare the similarity among Belgian samples, some human referenced specimens on the EWET database (EmsB Website for the Echinococcus Typing) and previously published EmsB profiles from red foxes circulating in/near Belgium. According to a comparison with human European specimens previously genotyped in profiles, the 18 Belgian ones were classified into three EmsB profiles. Four specimens could not be assigned to an already known profile but some are near to EWET referenced samples. This study also highlights that some specimens share the same EmsB profile with profiles characterized in red foxes from north Belgium, the Netherlands, Luxembourg and French department near to the Belgian border. Furthermore, Belgian specimens present a genetic diversity and include one profile that don't share similarities with the ones referenced in the EWET database. However, at this geographical scale, there is no clear correlation between EmsB profiles and geographical location. Further studies including additional clinical samples and isolates from foxes and rodents of south Belgium are necessary to better understand the spatial and temporal circumstances of human infections but also a potential correlation between EmsB profiles and parasite virulence

Macrophage-infectivity potentiator of Trypanosoma cruzi (TcMIP) is a new pro-type 1 immuno-stimulating protein for neonatal human cells and vaccines in mice.

peer reviewedThis work identifies the protein "macrophage infectivity potentiator" of Trypanosoma cruzi trypomastigotes, as supporting a new property, namely a pro-type 1 immunostimulatory activity on neonatal cells. In its recombinant form (rTcMIP), this protein triggers the secretion of the chemokines CCL2 and CCL3 by human umbilical cord blood cells from healthy newborns, after 24h in vitro culture. Further stimulation for 72h results in secretion of IFN-γ, provided cultures are supplemented with IL-2 and IL-18. rTcMIP activity is totally abolished by protease treatment and is not associated with its peptidyl-prolyl cis-trans isomerase enzymatic activity. The ability of rTcMIP to act as adjuvant was studied in vivo in neonatal mouse immunization models, using acellular diphtheria-tetanus-pertussis-vaccine (DTPa) or ovalbumin, and compared to the classical alum adjuvant. As compared to the latter, rTcMIP increases the IgG antibody response towards several antigens meanwhile skewing antibody production towards the Th-1 dependent IgG2a isotype. The amplitude of the rTcMIP adjuvant effect varied depending on the antigen and the co-presence of alum. rTcMIP did by contrast not increase the IgE response to OVA combined with alum. The discovery of the rTcMIP immunostimulatory effect on neonatal cells opens new possibilities for potential use as pro-type 1 adjuvant for neonatal vaccines. This, in turn, may facilitate the development of more efficient vaccines that can be given at birth, reducing infection associated morbidity and mortality which are the highest in the first weeks after birth

Maternal Infection with Trypanosoma cruzi and Congenital Chagas Disease Induce a Trend to a Type 1 Polarization of Infant Immune Responses to Vaccines

Vaccines are of crucial importance to prevent morbidity and mortality due to infectious diseases in childhood. A modulation of the fetal/neonatal immune system (considered immature) toward Th1 or Th2 dominance could modify responses to vaccines administered in early life. T. cruzi is the agent of Chagas' disease, in Latin America currently infecting about 2 million women at fertile ages who are susceptible to transmitting the parasite to their fetus. In previous studies we showed that T. cruzi-infected mothers can induce a pro-inflammatory environment in their uninfected neonates (M+B−), whereas congenitally infected newborns (M+B+) are able to develop a pro-Th1 parasite-specific T cell response. In the present study, we analysed the cellular and/or antibody responses to Bacillus Calmette Guerin (BCG), hepatitis B birus (HBV), diphtheria and tetanus vaccines in 6- to 7-month-old infants living in Bolivia. M+B− infants produced more IFN-γ in response to BCG, whereas M+B+ infants developed a stronger IFN-γ response to hepatitis B, diphtheria and tetanus vaccines and enhanced antibody production to HBs antigen. These results show that both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the neonatal period and that T. cruzi infection in early life tends to favour type 1 immune responses to vaccinal antigens

Facteur de nécrose tumorale, interleukine-6 et réaction inflammatoire dans l'infection expérimentale à "Trypanosoma cruzi"

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Maternal-Fetal Transmission of Trypanosoma cruzi

Maternal fetal transmission of T. cruzi can have severe outcomes by compromising survival and fetal/neonatal growth, and/or can lead to severe clinical forms of chronic infection later in adult life if an infant remains untreated. Congenital T. cruzi infection can be found worldwide since such transmission can occur in endemic areas, as well as nonendemic areas receiving immigrants from endemic regions. Though often asymptomatic at birth and neglected, this congenital infection must be considered an important public health problem requiring the development of reasonable prevention or control strategies, based on a deep understanding of mechanisms and multiple involved factors. Primary prevention (prophylaxis) of fetal infection with T. cruzi aims to prevent infection of pregnant women. This can be obtained by limiting the risk of contamination through vectorial contacts or blood transfusion, and by treating infected girls before they enter into their childbearing years. Secondary prophylaxis aims to avoid maternal-fetal parasite transmission from a previously infected pregnant woman using trypanocidal safe drugs. However, the potential teratogenic effects of both currently used trypanocidal drugs, benznidazole and nifurtimox, are not known. Their side effects in adults are unacceptable during pregnancy and their curative efficacy is limited in the chronic phase of infection presented by most infected pregnant women. For all these reasons, the treatment of T. cruzi infection during pregnancy is not recommended. © 2010 Elsevier Inc. All rights reserved.info:eu-repo/semantics/publishe

Protective host response to parasite and its limitations

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