Demonstration of the presence of IL-16, IL-17 and IL-18 at the murine fetomaternal interface during murine pregnancy

PROBLEM: To determine if interleukin-16 (IL-16), IL-17, and IL-18 are present at the murine fetomaternal interface during pregnancy as a first step towards investigating their roles in fetomaternal relationship. METHODS: Expression of IL-16, IL-17, and IL-18, was assessed by immunohistochemistry (IHC) in the BALB/c x BALB/k (H2d x H2k), and the CBA/J x BALB/c non-abortion prone, and CBA/J x DBA/2 abortion prone matings. Enzyme-linked immunosorbent assay (ELISA) were performed for the two latter cytokines to compare local production in the abortion prone CBA/J x DBA/2 versus the non-abortion prone CBA/J x BALB/c matings. RESULTS: Expression of IL-17 was borderline. The anti-IL-16 staining specifically localized in the uterine stroma and glandular epithelium and was rather low in the placenta. IL-18 staining started in the peri-implantation uterus in the basal proliferative stroma, and was also traced, although weaker, in the glandular epithelium. In the immediate post-implantation period, a weak stromal staining persisted but there was a strong labeling of the ectoplacental cone. Interestingly, when the ectoplacental cone differentiates into placenta having a major histocompatibility complex (MHC) class I + spongiotrophoblast and a (MHC class I-) labyrinth, a very strong transient labeling of uterine natural killer (u-NK) cells was found. Later in gestation, IL-18 was also produced by giant cell and spongiotrophoblast. Finally, we compared by ELISA the production of IL-17/-18 in CBA/J x DBA/2 and CBA/J x BALB/c matings. We detected significantly more IL-18 in the non-abortion prone combination decidua or placenta. CONCLUSION: The three cytokines IL-16, IL-17, and IL-18 were detected at the fetomaternal interface with a tissue specific, stage-dependent distribution. The predominance of IL-18 secretion in the non-resorption prone matings lead us to question the general validity of the classical T-helper (Th)1/2 paradigm.     

Congenital parasitic infections: a review

This review defines the concepts of maternal-fetal (congenital) and vertical transmissions (mother-to-child) of pathogens and specifies the human parasites susceptible to be congenitally transferred. It highlights the epidemiological features of this transmission mode for the three main congenital parasitic infections due to Toxoplasma gondii, Trypanosoma cruzi and Plasmodium sp. Information on the possible maternal-fetal routes of transmission, the placental responses to infection and timing of parasite transmission are synthesized and compared. The factors susceptible to be involved in parasite transmission and development of congenital parasitic diseases, such as the parasite genotypes, the maternal co-infections and parasitic load, the immunological features of pregnant women and the capacity of some fetuses/neonates to overcome their immunological immaturity to mount an immune response against the transmitted parasites are also discussed and compared. Analysis of clinical data indicates that parasitic congenital infections are often asymptomatic, whereas symptomatic newborns generally display non-specific symptoms. The long-term consequences of congenital infections are also mentioned, such as the imprinting of neonatal immune system and the possible trans-generational transmission. The detection of infection in pregnant women is mainly based on standard serological or parasitological investigations. Amniocentesis and cordocentesis can be used for the detection of some fetal infections. The neonatal infection can be assessed using parasitological, molecular or immunological methods; the place of PCR in such neonatal diagnosis is discussed. When such laboratory diagnosis is not possible at birth or in the first weeks of life, standard serological investigations can also be performed 8-10 months after birth, to avoid detection of maternal transmitted antibodies. The specific aspects of treatment of T. gondii, T. cruzi and Plasmodium congenital infections are mentioned. The possibilities of primary and secondary prophylaxes, as well as the available WHO corresponding recommendations are also presented.     

A new PCR-ELISA for diagnosis of visceral leishmaniasis in blood of HIV-negative subjects

The PCR-ELISA represents a promising advance for diagnosis of visceral leishmaniasis (VL) in blood samples. However, the method has been validated mostly with HIV-positive patients who are known to have high levels of parasitaemia. We developed a new PCR-ELISA assay for specific detection of Leishmania in patients' blood and validated it in Nepalese subjects with clinically suspected VL, almost all of whom were HIV-negative. For blood samples, PCR-ELISA was more sensitive (83.9%) than conventional PCR (73.2%), and demonstrated 100% and 87.2% specificity when using healthy controls who had never travelled to a VL-endemic area and controls from a VL-endemic area as references, respectively. We have demonstrated the ability of PCR-ELISA to detect parasites in blood of HIV-negative patients. The method could be used for epidemiological as well as clinical purposes, as it reduces the need for traumatic bone marrow sampling and risky spleen aspiration.     

Acute Trypanosoma cruzi infection: IL-12, IL-18, TNF, sTNFR and NO in T. rangeli-vaccinated mice

We have developed an experimental model of vaccination against the infection with the protozoa Trypanosoma cruzi, the agent of Chagas disease in Latin America. Vaccination was performed with Trypanosoma rangeli, a non-pathogenic protozoa sharing many antigens with T. cruzi. It strongly protected BALB/c mice, sharply reducing parasitaemia and mortality rate of the acute T. cruzi infection. The aim of the present work was to complete our previous study on the production of IFN-gamma and IL-10 in this vaccination model by investigating the production of IL-12p35 and p40, IL-18, TNF, TNF soluble receptors (sTNFR), and nitric oxide (NO), factors known to play a key role in the outcome of T. cruzi infection. We show that the protection obtained against the acute T. cruzi infection was surprisingly associated with reduced circulating levels of IL-18 and NO, whereas the release of IL-12p40 was enhanced in comparison to non-vaccinated infected animals. IL-12p35 remained undetectable in infected animals, vaccinated or not. The balance between sTNFR and TNF suggested a decrease of TNF bioactivity in vaccinated mice. These results show that the protection induced by the vaccination with T. rangeli against a challenging infection with T. cruzi is not associated with the strong type 1 immune response usually involved in the control of intracellular pathogens, particularly questioning the protective role of NO during the acute phase of T. cruzi infection.     

Four infants with congenital cystic malformation of the lung: different routes of diagnosis and forms of management

In four neonates, two boys and two girls, congenital cystic malformation of the lung was diagnosed. Two cases were diagnosed during prenatal ultrasound investigation. One of the patients recovered by a wait-and-see policy, one after antibiotic treatment and two following surgical removal of the diseased lung sections. Congenital pulmonary cysts are rare; congenital cystadenomatoid malformation (CCAM) is the most prevalent form. The most common presentation of CCAM is respiratory distress immediately following birth. Some children are asymptomatic at birth, but present with recurrent respiratory infections later in childhood. With the increasing use of antenatal ultrasound, an increasing number of cystic lung lesions are diagnosed antenatally. The prognosis of these mostly asymptomatic lesions is not clear and indications for prenatal and postnatal interventions must be determined by a multidisciplinary approach. Recently, malignant pulmonary tumours were found to be associated with CCAM. This finding necessitates long-term follow-up, even of asymptomatic CCAM lesions.     

Vaccination with Trypanosoma rangeli reduces the infectiousness of dogs experimentally infected with Trypanosoma cruzi

The goal of this work was to test the efficacy of the vaccination with Trypanosoma rangeli in dogs. Mongrel dogs received three subcutaneous injections of fixed T. rangeli epimastigotes at 6-week intervals. Such immunisation induced antibodies against Trypanosoma cruzi. While both control and immunised dogs developed detectable parasitemia, this was lower and shorter in vaccinated animals. Interestingly, feeding of Triatoma infestans nymphs on vaccinated and chronically infected dogs led to a sharp reduction in the rate of bug infection. These results suggest that it might be possible to reduce the vectorial parasitemia through vaccination of dogs. As dogs are known to play a major role in the domestic cycle of T. cruzi, this might represent a strategy to reduce parasite transmission to humans.     

Human fetuses are able to mount an adultlike CD8 T-cell response

Fetal/neonatal immune responses generally are considered to be immature and weaker than that of adults. We have studied the cord-blood T cells of newborns congenitally infected with Trypanosoma cruzi, the protozoan agent of Chagas disease. Our data demonstrate a predominant activation of CD8 T cells expressing activation markers and armed to mediate effector functions. The analysis of the T-cell receptor beta chain variable repertoire shows the oligoclonal expansion of these T lymphocytes, indicating that activation was driven by parasite antigens. Indeed, we have detected parasite-specific CD8 T cells secreting interferon-gamma after coincubation with live T cruzi. This response is enhanced in the presence of recombinant interleukin-15, which limits the T-cell spontaneous apoptosis. These findings point out that the fetal immune system is more competent than previously appreciated, since fetuses exposed to live pathogens are able to develop an adultlike immune CD8 T-cell response.     

Microbial ecology of the closed artificial ecosystem MELiSSA (Micro-Ecological Life Support System Alternative): reinventing and compartmentalizing the Earth's food and oxygen regeneration system for long-haul space exploration missions

MELiSSA is a bioregenerative life support system designed by the European Space Agency (ESA) for the complete recycling of gas, liquid and solid wastes during long distance space exploration. The system uses the combined activity of different living organisms: microbial cultures in bioreactors, a plant compartment and a human crew. In this minireview, the development of a short-cut ecological system for the biotransformation of organic waste is discussed from a microorganism's perspective. The artificial ecological model--still in full development--that is inspired by Earth's own geomicrobiological ecosystem serves as an ideal study object on microbial ecology and will become an indispensable travel companion in manned space exploration.