Zinc Supplementation: Immune Balance of Pregnancy During the Chronic Phase of the Chagas Disease.

BACKGROUND: Chagas disease or American trypanosomiasis is caused by the protozoan Trypanosoma cruzi and is endemic of the Americas. The control of the disease is restricted to toxic and potentially teratogenic drugs, which limit the use during pregnancy. The use of food supplementation offers a safe and low-cost form to alleviate Chagas disease symptoms, mostly in areas with alimentary risk. For example, zinc demonstrates positive effects in immune response, including in Chagas disease during pregnancy. PURPOSE: This study describes the innate response in pregnant rats chronically infected with T. cruzi and supplemented with zinc. METHODS: Pregnant female Wistar rats, infected with T. cruzi, were treated with 20 mg/kg/day zinc sulfate and euthanized on the 18th day. Samples (plasma, splenocytes, and peritoneal exudate) were collected and several immune parameters (nitric oxide, RT1B, CD80/CD86, MCP-1, CD11b/c, NK/NKT, IL-2, IL-10, INF-cc, and apoptosis) evaluated. RESULTS: Under Zinc supplementation and/or T. cruzi infection, the gestation developed normally. Several innate immune parameters such as RT1B, CD80/CD86, MCP-1 expressing lymphocytes, IL-2, and IL-17 were positively altered, whereas nitric oxide, CD11b/c, NK/NKT, apoptosis, INF-γ, and corticosterone demonstrated a pro-pregnancy pattern. CONCLUSION: Our results indicated that zinc has diverse effects on immune response during pregnancy. An anti-T. cruzi immunity, as well as a pro-gestation response, were observed after zinc supplementation. The complete comprehension of zinc supplementation in pregnancy will base an adequate strategy to alleviate Chagas disease symptoms and propagation, especially for populations from endemic areas.

The treatment with selenium increases placental parasitismin pregnant Wistar rats infected with the Y strain of Trypanosoma cruzi.

Selenium (Se) is an essential micronutrient in the diet of mammals and has an important role in the immune function. Selenium is a key element in selenoproteins involved in the in the maintenance of the antioxidant defense. Diet with selenium is beneficial for the treatment of diseases correlated with high levels of oxidative stress, also observed in the Chagas disease. Chagas disease is a neglected disease caused by the protozoan Trypanosoma cruzi and several research groups are focused on the illness treatment. Immunomodulation of the infection using microelements is an important tool to avoid deleterious effects of the Chagas disease. Therefore, our objective was to evaluate the effects of selenium supplementation on pregnant Wistar rats infected with T. cruzi. Selenium treatment stimulated the weight and length of fetuses and placentas allied to the decrease of blood parasitemia. However, selenium demonstrated a low influence on T cells, diminishing the B cell population (CD45RA+). Moreover, the production of pro-inflammatory cytokines was downregulated under selenium administration. Low pro-inflammatory cytokines levels probably are related to the increase in the number of amastigote nests in infected and treated animals. Thus, selenium supplementation during pregnancy could impair the local placental immune response. Further studies are necessary to assess the interaction between selenium and the acute Chagas' disease during pregnancy, which will base future supplementation strategies.

Is the adaptive immune response in murine Trypanosoma cruzi infection influenced by zinc supplementation?

Chagas disease afflicts 7 to 8 million people worldwide and congenital Chagas' disease usually leads to changes in the maternal environment, culminating in fetal adaptations. Several articles have described the importance of micronutrients on pregnancy, which is sensitive to infections. In Trypanosoma cruzi endemic regions, the Chagas disease is aggravated by the lack of micronutrients in an average diet, to which pregnant women are more susceptible. The aim of this study was to evaluate distinct T cells phenotypes and intracellular cytokines by flow cytometry in pregnant Wistar rats under zinc therapy during experimental Chagas' disease. Twenty female Wistar rats were infected with 1×105 blood trypomastigotes (Y strain) and 30days after infection the animals were mated and grouped: pregnant infected (PI-n=5), pregnant infected/zinc supplied (PIZ-n=5), pregnant control (PC-n=5), control/zinc supplied (PCZ-n=5). Zinc supplementation: 20mg of zinc/Kg/day (gavage) for 18days followed by euthanasia. The immune parameters showed: decreased percentages of CD62LlowCD44high surface marker for infected and treated group (PIZ) when compared to PI (p<0.05). Concerning to T regulatory cells (Treg cells), a significantly lower percentage of splenic Treg cells was found in the infected and treated group (PIZ) as compared to the PI group (p<0.05). The expression of the co-stimulatory molecule CD28+ displayed a significant reduced percentage in TCD8+ for infected and zinc treated group (PIZ) as compared to (PI). The percentages of CD4+/CD11a+ T cells subsets were lower on PIZ as compared to PI. Concerning to CD45RA+ (B lymphocytes) analysis, infected pregnant and treated group (PIZ) showed a significant decrease in CD45RA percentage when compared to (PI) (p<0.05). The intracellular cytokine profiles for TCD4+ and TCD8+ producing IL-4 and IFN-γ revealed that zinc treated and untreated infected pregnant group (PI and PIZ) displayed increased cytokines concentrations as compared to zinc treated and untreated pregnant controls (PC and PCZ). Our data revealed the involvement of zinc as a signaling molecule in the modulation of the inflammatory process and immune response which occurs during pregnancy of T. cruzi infected rats. Zinc acted in a dual fashion, modulating the host's immune response in a way to protect the organism against the deleterious effects of the infection and an overwhelming pro-inflammatory response during pregnancy.

Does L-arginine availability during the early pregnancy alters the immune response of Trypanosoma cruzi infected and pregnant Wistar rats?

Chagas disease induces a strong immune response and L-arginine is an essential amino acid which plays an important role in homeostasis of the immune system. The aims of this study were to evaluate parasitemia, corticosterone levels, production of nitric oxide (NO), fetal morphological measurements, and histology of heart and placenta. Twenty pregnant Wistar rats (180-220 g) were grouped in: pregnant control (PC), pregnant control and L-arginine supplied (PCA), pregnant infected (PI), pregnant infected and L-arginine supplied (PIA). Females were infected with 1×10(5) trypomastigotes of the Y strain (3rd day of pregnancy). Animals were supplied with 21 mg of L-arginine/kg/day during 14 days. PIA showed significant decreased levels of corticosterone and parasitemia. For control groups, any alteration in NO production was found with L-arginine supplementation; for PIA, enhanced nitrite concentrations were observed as compared to PI. Weights and lengths of fetuses were higher in L-arginine treated and infected pregnant rats as compared to untreated ones. Placental weight from the PIA group was significantly increased when compared to PI. In L-arginine treated animals, cardiac tissue showed reduced amastigote burdens. PIA and PI displayed similar placental parasitism. Based on these results, L-arginine supplementation may be potentially useful for the protection against Trypanosoma cruzi during pregnancy.