Anti-Toxoplasma gondii IgM Long Persistence: What Are the Underlying Mechanisms?

Diagnosis of Toxoplasma gondii acute infection was first attempted by detection of specific IgM antibodies, as for other infectious diseases. However, it was noted that this immunoglobulin declines slowly and may last for months or even years. Apart from the diagnostic problem imposed on clinical management, this phenomenon called our attention due to the underlying phenomena that may be causing it. We performed a systematic comparison of reports studying IgM antibody kinetics, and the data from the papers were used to construct comparative plots and other graph types. It became clear that this phenomenon is quite generalized, and it may also occur in animals. Moreover, this is not a technical issue, although some tests make more evident the prolonged IgM decay than others. We further investigated biological reasons for its occurrence, i.e., infection dynamics (micro-reactivation-encystment, reinfection and reactivation), parasite strain relevance, as well as host innate, natural B cell responses and Ig class-switch problems inflicted by the parasite. The outcomes of these inquiries are presented and discussed herein.

Microbiota Signals during the Neonatal Period Forge Life-Long Immune Responses.

The microbiota regulates immunological development during early human life, with long-term effects on health and disease. Microbial products include short-chain fatty acids (SCFAs), formyl peptides (FPs), polysaccharide A (PSA), polyamines (PAs), sphingolipids (SLPs) and aryl hydrocarbon receptor (AhR) ligands. Anti-inflammatory SCFAs are produced by Actinobacteria, Bacteroidetes, Firmicutes, Spirochaetes and Verrucomicrobia by undigested-carbohydrate fermentation. Thus, fiber amount and type determine their occurrence. FPs bind receptors from the pattern recognition family, those from commensal bacteria induce a different response than those from pathogens. PSA is a capsular polysaccharide from B. fragilis stimulating immunoregulatory protein expression, promoting IL-2, STAT1 and STAT4 gene expression, affecting cytokine production and response modulation. PAs interact with neonatal immunity, contribute to gut maturation, modulate the gut-brain axis and regulate host immunity. SLPs are composed of a sphingoid attached to a fatty acid. Prokaryotic SLPs are mostly found in anaerobes. SLPs are involved in proliferation, apoptosis and immune regulation as signaling molecules. The AhR is a transcription factor regulating development, reproduction and metabolism. AhR binds many ligands due to its promiscuous binding site. It participates in immune tolerance, involving lymphocytes and antigen-presenting cells during early development in exposed humans.

Report of an unsual case of anophthalmia and craniofacial cleft in a newborn with Toxoplasma gondii congenital infection.

BACKGROUND: We present one unusual case of anophthalmia and craniofacial cleft, probably due to congenital toxoplasmosis only. CASE PRESENTATION: A two-month-old male had a twin in utero who disappeared between the 7th and the 14th week of gestation. At birth, the baby presented anophthalmia and craniofacial cleft, and no sign compatible with genetic or exposition/deficiency problems, like the Wolf-Hirschhorn syndrome or maternal vitamin A deficiency. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neo-antibodies in western blot, as well as by real time PCR in blood. CMV infection was also discarded by PCR and IgM negative results. Structures suggestive of T. gondii pseudocysts were observed in a biopsy taken during the first functional/esthetic surgery. CONCLUSIONS: We conclude that this is a rare case of anophthalmia combined with craniofacial cleft due to congenital toxoplasmosis, that must be considered by physicians. This has not been reported before.

Vertical transmission and fetal damage in animal models of congenital toxoplasmosis: A systematic review.

In humans, the probability of congenital infection and fetal damage due to Toxoplasma gondii is dependent on the gestation period at which primary infection occurs. Many animal models have been used for vaccine, drug testing, or studies on host or parasite factors that affect transmission or fetal pathology, but few works have directly tested fetal infection and damage rates along gestation. So, the purpose of this work was to perform a systematic review of the literature to determine if there is a model which reflects these changes as they occur in humans. We looked for papers appearing between 1970 and 2014 in major databases like Medline and Scopus, as well as gray literature. From almost 11,000 citations obtained, only 49 papers fulfilled the criteria of having data of all independent variables and at least one dependent datum for control (untreated) groups. Some interesting findings could be extracted. For example, pigs seem resistant and sheep susceptible to congenital infection. Also, oocysts cause more congenitally infected offspring than tissue cysts, bradyzoites or tachyzoites. In spite of these interesting findings, very few results on vertical transmission or fetal damage rates were similar to those described for humans and only for one of the gestation thirds, not all. Moreover, in most designs tissue cysts - with unknown number of bradyzoites - were used, so actual dose could not be established. The meta-analysis could not be performed, mainly because of great heterogeneity in experimental conditions. Nevertheless, results gathered suggest that a model could be designed to represent the increase in vertical transmission and decrease in fetal damage found in humans under natural conditions.

Seroprevalence and national distribution of human toxoplasmosis in Mexico: analysis of the 2000 and 2006 National Health Surveys.

Global warming has had serious implications on dispersion of infectious diseases like toxoplasmosis. Since the frequency of Toxoplasma gondii largely depends on climatic conditions, we studied its prevalence by means of 3599 samples of the National Health Survey 2000 (NHS-2000) and 2916 of the National Health and Nutrition Survey 2006 (NHNS-2006) serum banks, obtained from 1-98 year old subjects of both genders and all states of Mexico. Anti-T.gondii IgG antibodies were determined by ELISA and confirmed by western blot. Crude, epidemiologically weighted and diagnosis-performance-adjusted prevalence values were calculated. Seroprevalence changes were compared between both surveys and among regions (north, center and coast). Also, correlations between changes in temperature or humidity and those in prevalence were measured. National crude prevalence was 60.1% and 62.6% for NHS-2000 and NHNS-2006, respectively. Weighted and adjusted values were 62.5% and 40.0% for NHS-2000, and 63.7 and 43.1% for NHNS-2006. Coastal states and children presented the largest increases between surveys, while the center of the country showed a decrease. An apparently higher prevalence of T. gondii infection was observed in both surveys compared to that performed in 1987, while a geographical re-distribution was found from 2000 to 2006, with a positive correlation between temperature and frequency deltas in 21 states where prevalence increased.

Parasiticidal effect of 16alpha-bromoepiandrosterone (EpiBr) in amoebiasis and cysticercosis.

The effect of the dehydroepiandrosterone analog 16alpha-bromoepiandrosterone (EpiBr) was tested on the tapeworm Taenia crassiceps and the protist Entamoeba histolytica, both in vivo and in vitro. Administration of EpiBr prior to infection with cysticerci in mice reduced the parasite load by 50% compared with controls. EpiBr treatment induced 20% reduction on the development of amoebic liver abscesses in hamsters. In vitro treatment of T. crassiceps and E. histolytica cultures with EpiBr, reduced reproduction, motility and viability in a dose- and time-dependent fashion. These results leave open the possibility of assessing the potential of this hormonal analog as a possible anti-parasite drug, including cysticercosis and amoebiasis.

Immunoendocrine mechanisms associated with resistance or susceptibility to parasitic diseases during pregnancy.

During pregnancy, the mammalian endocrine system plays a leading role in maintaining the fetus, characterized by an increase in the level of hormones such as progesterone, oestradiol and some gonadotropic hormones. The immune system participates during pregnancy by self-regulating to prevent fetus rejection. The distinctive type of immunity during gestation is characterized by an increase in levels of Th2 type cytokines IL-4, IL-6 and IL-10, concomitant with a decrease in IL-2, INF-gamma and TNF-alpha levels. Along pregnancy, sex steroids and factors associated with them regulate the immune response. In this way, endocrine and immunologic factors have an impact on the pregnant female's susceptibility or resistance to parasitic diseases. There are three main mechanisms proposed to explain this susceptibility or resistance: (1) sex steroids influence the host's immune system; (2) hormones acting directly on the parasites inhibit or promote their reproduction, or (3) the two effects can occur simultaneously within a network of immuno-endocrine host-parasite interactions, mediated by hormones, cytokines, antibodies and other factors interacting directly and bidirectionally. The present work reviews recent literature concerning the most frequent parasitic infections during pregnancy and discusses the mechanisms implied in the establishment, growth, reproduction or elimination of the parasite.

Taenia crassiceps infection disrupts estrous cycle and reproductive behavior in BALB/c female mice.

Previously, it has been shown that parasitic infections are able to alter the normal mammal physiology, at several extents. Thus, we investigated the effects on estrous cycle and sexual behavior induced by intraperitoneal infection with Taenia crassiceps in female host mice. Along the weeks of infection, parasites were collected from the peritoneal cavity of female mice, showing the maximum parasite load at 16 weeks. No parasites were found outside peritoneal cavity. Vaginal estrous cycle was monitored daily for 4, 8, 12 and 16 weeks of infection, and results compared against age-matched female mice. Female sexual behavior (FSB) tests were performed, one test per week. Immediately after the last behavioral test, blood was collected by cardiac puncture for steroid determinations. First of all, there was a strong tissular damage in the female reproductive tract in all infected females. The phases of the estrous cycle were interrupted at 12 and 16 weeks, with increased leukocytes and the presence of a few cornified epithelial cells and nucleated epithelial cells. The FSB decreased starting 6 weeks post infection. On the 16th week, all infected female mice ceased to exhibit sexual responses, and estradiol levels showed a significant decrease. Control mice continued showing FSB and the different phases of the estrous cycle throughout the observation period. Our results strength the notion that parasites may be considered as an evolutionary force in the reproductive ability of mammals.

Treatment with dehydroepiandrosterone in vivo and in vitro inhibits reproduction, growth and viability of Taenia crassiceps metacestodes.

The aim of this work was to explore the effect of dehydroepiandrosterone (DHEA) on the establishment, growth and reproduction of the metacestode stage of the tapeworm Taenia crassiceps, both in vivo and in vitro. Administration of DHEA prior to infection in mice of both sexes reduced the parasite load by 50% compared with untreated mice. This protective effect was not associated with the immune response, since there was no effect of DHEA treatment on mRNA levels of IL-2, IFN-gamma, IL-4 or IL-10. DHEA treatment of infected mice increased androgen receptor expression in splenocytes of both sexes. Moreover, in vitro treatment of T. crassiceps with DHEA reduced reproduction, motility and viability in a dose- and time-dependent fashion. Results indicate that DHEA has strong negative direct modulatory effects on murine cysticercosis. We suggest the use of hormonal-analogues for protective purposes as a therapeutic approach to prevent murine cysticercosis.

[Pregnancy, acquired immunity and parasitic diseases: main mechanisms associated to resistance or susceptibility]. / Embarazo inmunidad adquirida y enfermedades parasitarias: principales mecanismos asociados a la resistencia o susceptibilidad.

During pregnancy in mammals, the endocrine system plays a protagonic role, characterized by variation of different hormonal serum levels, such as estradiol, progesterone and some gonadotrophic hormones. Furthermore, the immunological system also participates during pregnancy, self-regulation for to avoid not rejecting the fetus. The characteristic immunity during the pregnancy is the humoral type: which is characterized by an increase in the levels of the Th-2 type cytokines IL-4, IL-6, IL-10, concomitant to a diminution in the levels of IL-2, INF-gamma and TNF-alpha The type of immunological response present during the pregnancy is mainly regulated by mechanisms associated to sexual hormones. This particular immunological response during the pregnancy, has individual importance if an infectious disease appears, since, depending on the parasite, a susceptibility or a resistance to the infection can exist. The proposed mechanisms to explain this resistance or susceptibility can be one of the following: (1) the hormones are influencing the immunological system of the host (by means of specific nuclear receptors); (2) the hormones acting directly on the parasite, preventing or promoting their reproduction and (3) a combination of both. These mechanisms support the idea of a complex immunoendocrine network (mediated by hormonal receptors, citokynes, antibodies) in host and parasite, interacting in a bidirectional way. The final outcome of this interaction is the death or survival of the host, or the parasite. In this review, we evaluate the information about the more frequent parasitic infections during pregnancy, and discuss the implied molecular mechanisms that affects the establishment, growth, reproduction or elimination of the parasite.