concanavalin-a and Parasitemia

Chagas disease is a neglected tropical disease. The ability of Trypanosoma cruzi to survive within phagocytes is likely a critical factor for T. cruzi dissemination in the host. For control of the parasite load and host survival, macrophage action is required. Concanavalin-A (Con-A) presents properties that modulate immune functions and protect hosts from several experimental infectious diseases. Here, we evaluated the effects of Con-A on peritoneal macrophages as well as on the course of experimental infection by T. cruzi.. BALB/c mice, a susceptible model for T. cruzi infection, were treated with Con-A via the intraperitoneal route and 3 days later infected with T. cruzi. We quantified parasitemia, cytokines and nitric oxide (NO). Peritoneal exudate and macrophages were collected for macrophage phenotyping and cell viability, NO and cytokine detection, as well as for T. cruzi internalization and release index determination.. Con-A treatment induced IL-17a and NO production by cells from the peritoneal cavity, and M1 marker expression predominated on peritoneal macrophages. These cells are also more prone to producing TNF-α, IL-6 and NO when infected by T. cruzi and show high trypanocidal capacity. Due to a hostile peritoneal microenvironment caused by Con-A, which induces macrophage cNOS and iNOS expression, infected BALB/c mice showed reduced parasitemia and an increased survival rate.. We conclude that Con-A can induce peritoneal M1 macrophage polarization to increase trypanocidal activity, resulting in ameliorated systemic infection in a susceptible experimental model.

Topics: Animals; Cell Polarity; Chagas Disease; Concanavalin A; Female; Interleukin-17; Macrophages, Peritoneal; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Synthase Type II; Parasitemia; Trypanosoma cruzi

During the course of infection by Trypanosoma cruzi, the host immune system is involved in distinct, complex interactions with the endocrine system, and prolactin (PRL) is one of several hormones involved in immunoregulation. Although intensive studies attempting to understand the mechanisms that underlie Chagas' disease have been undertaken, there are still some pieces missing from this complex puzzle. Because data are scarce concerning the role of PRL involvement in Chagas' disease and taking into account the existence of crosstalk between neuroendocrine hormones and the immune system, the current study evaluates a possible up-regulation of the cellular immune response triggered by PRL in T. cruzi-infected rats and the role of PRL in reversing immunosuppression caused by the parasitic infection. The data shown herein demonstrate that PRL induces the proliferation of T lymphocytes, coupled with an activation of macrophages and the production of nitric oxide (NO), leading to a reduction in the number of blood trypomastigotes during the peak of parasitemia. During the acute phase of T. cruzi infection, an enhancement of both CD3+CD4+ and CD3+CD8+ T cell populations were observed in infected groups, with the highest numbers of these T cell subsets found in the infected group treated with PRL. Because NO is a signaling molecule involved in a number of cellular interactions with components of the immune system and the neuroendocrine system, PRL can be considered an alternative hormone able to up-regulate the host's immune system, consequently lowering the pathological effects of a T. cruzi infection.

Topics: Animals; Cell Proliferation; Chagas Disease; Concanavalin A; Flow Cytometry; Immunity, Innate; Lipopolysaccharides; Macrophages, Peritoneal; Male; Nitric Oxide; Parasitemia; Prolactin; Rats; Rats, Wistar; T-Lymphocyte Subsets; Thymocytes; Trypanosoma cruzi; Up-Regulation

Melatonin by exhibiting antioxidant, anti-aging, and immunomodulatory properties favorably modulate the immune function, protecting the hosts from several infectious diseases. Zinc is an essential trace element important for the efficiency of the immune system in reason of its widespread role in the activity of enzymes, transcription factors and cytokines. The etiology of Chagas' disease, caused by a protozoan parasite Trypanosoma cruzi, has been the focus of considerable discussion, although chronic phase still remains not fully understood. This study showed that zinc and melatonin treatment did not affect the percentage of both CD4+ and CD8+ T lymphocytes subsets in chronically infected animals. Increased levels of IL-2 and IL-10, as well as, enhanced thymocyte proliferation in T. cruzi infected groups under zinc and melatonin therapy was observed as compared to untreated group. Conversely, during the chronic phase of infection, macrophages counts were reduced in melatonin and zinc-melatonin treated animals. The combined actions of zinc and melatonin have beneficial effects in counteracting parasite-induced immune dysregulation, protecting animals against the harmful actions of chronic T. cruzi infection. Furthermore, our results provide an experimental basis for further studies on the role of immunomodulatory therapies.

Topics: Animals; Antigens, CD; Cell Count; Cell Proliferation; Chagas Disease; Chronic Disease; Concanavalin A; Cytokines; Interleukin-10; Interleukin-2; Macrophages, Peritoneal; Male; Melatonin; Parasitemia; Phenotype; Rats; Rats, Wistar; Thymocytes; Trypanosoma cruzi; Zinc

Malaria and intestinal nematode infection are widespread and co-infection frequently occurs. We investigated whether co-infected intestinal nematodes modulate immunity against co-existing malaria parasites. Infection of C57BL/6 mice with Plasmodium yoelii 17XNL (Py) was transient and self-limiting, but preceding infection with Heligmosomoides polygyrus (Hp), a mouse intestinal nematode, exacerbated malaria resulting in higher parasite burdens and poor survival of the mice. Co-infection with Hp led to reduced Py-responsive proliferation and IFN-gamma production of spleen cells, and higher activation of CD4(+)CD25(+)Foxp3(+) Treg. In vivo depletion of Treg recovered anti-Py immunity and rescued co-infected mice from exacerbated malaria. However, we did not observe any obvious ex vivo activation of Treg by either Hp products or living worms. Our results suggest that intestinal nematodes moderate host immune responses during acute malaria infection by aggressive activation of Treg. Elucidation of the mechanisms of Treg activation in situ is a target for future analyses.

Topics: Animals; Antibodies, Monoclonal; Antigens, Helminth; Cell Count; Concanavalin A; Dendritic Cells; Erythrocytes; Forkhead Transcription Factors; Immune Tolerance; Immunoglobulin G; Interferon-gamma; Interleukin-2 Receptor alpha Subunit; Lymphocyte Activation; Lymphocyte Depletion; Malaria; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Nematospiroides dubius; Parasitemia; Plasmodium yoelii; Spleen; Strongylida Infections; Survival Analysis; T-Lymphocytes, Regulatory

Control of the acute phase of Trypanosoma cruzi infection is critically dependent on cytokine-mediated macrophage activation to intracellular killing, natural killer (NK) cells, CD4(+) T cells, CD8(+) T cells and B cells. Cell-mediated immunity in T. cruzi infection is also modulated by cytokines, but in addition to parasite-specific responses, autoimmunity can be also triggered. Importantly, cytokines may also play a role in the cell-mediated immunity of infected subjects. Here we studied the role of cytokines in the regulation of innate and adaptive immunity during the acute phase of T. cruzi infection in Wistar rats. Melatonin is an effective regulator of the immune system. Macrophages and T lymphocytes, which have melatonin receptors, are target cells for the immunomodulatory function of melatonin. In this paper melatonin was orally given via two protocols: prior to and concomitant with infection. Both treatments were highly effective against T. cruzi with enhanced action for the concomitant treatment. The data suggest an up-regulation of the TH-1 immune response as all analyzed parameters, interleukin (IL)-4, IL-10, transforming growth factor-beta1 and splenocyte proliferation, displayed reduced levels as compared with the untreated counterparts. However, the direct effects of melatonin on immune cells have not been fully investigated during T. cruzi infection. We conclude that in light of the current results, melatonin exerted important therapeutic benefits through its immune regulatory effects.

Topics: Analysis of Variance; Animals; Chagas Disease; Concanavalin A; Cytokines; Immunity, Active; Immunity, Innate; Interleukin-10; Interleukin-4; Macrophages; Melatonin; Parasitemia; Rats; Rats, Wistar; Th1 Cells; Th2 Cells; Transforming Growth Factor beta; Trypanosoma cruzi

It is well recognized that zinc is an essential trace element for all organisms, influencing growth and affecting the development and integrity of the immune system. It is also well known that the protective response against Trypanosoma cruzi depends on both innate and acquired immunity and for the control of the parasite load and host survival, the participation of special cells such natural killer (NK), T and B lymphocytes and macrophages are required. So the aims of this study were to evaluate the effects of zinc supplementation on the host's immune response infected with T. cruzi. Our data point in the direction that zinc supplementation triggered enhanced thymocyte and splenocyte proliferation as compared to unsupplied group of animals. It is also important to emphasize that interleukin-12 (IL-12) participates in the resistance to several intracellular pathogens including T. cruzi. Our findings demonstrate an enhanced production of IL-12 during the acute phase of infection in zinc-supplied groups. So we conclude that zinc supplementation leads to an effective host's immune response by up-modulating the host's immune response, thus contributing in the reduction of blood parasites and the harmful pathogenic effects of the experimental Chagas' disease.

Topics: Animals; Concanavalin A; Interleukin-12; Male; Parasitemia; Rats; Rats, Wistar; Spleen; Thymus Gland; Time Factors; Trypanosoma cruzi; Trypanosomiasis; Zinc

We investigated the possible role of prostaglandins produced by COX-2 in the immunosuppression observed during Trypanosoma cruzi infection. Con-A-stimulated splenocytes isolated from mice on days 5, 10, and 15 of infection released large amounts of PGE2 and this release was inhibited by the treatment of animals with sodium salicylate or meloxicam. The treatment of the animals with these drugs enhanced the release of IL-2 by splenocytes from T. cruzi-infected animals and significantly reduced the blood parasitemia and delayed the mortality of the infected mice. Furthermore, the release of TNF-alpha, IFN-gamma, IL-4, and IL-10 by Con-A-stimulated splenocytes obtained from infected mice on days 5, 10, and 15 of the infection was significantly inhibited by treatment of the animals with salicylate or meloxicam. In conclusion, the results suggest that the prostaglandins produced mainly by COX-2 mediate the immunosuppression observed in the acute phase of T. cruzi infection.

Topics: Acute Disease; Animals; Cells, Cultured; Chagas Disease; Concanavalin A; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Cytokines; Dinoprostone; Immune Tolerance; Lymphocyte Activation; Male; Meloxicam; Mice; Mice, Inbred BALB C; Parasitemia; Prostaglandin-Endoperoxide Synthases; Sodium Salicylate; Spleen; T-Lymphocytes; Thiazines; Thiazoles

The relevance of trypanosome-induced immunosuppression in relation to the efficacy of vaccine-induced immunity was studied in mice. Mice were immunised with crude Trichinella spiralis muscle larvae homogenate vaccine and infected with T. spiralis and/or Trypanosoma brucei. Vaccination significantly decreased adult worm burden (p<0. 05) and accelerated worm expulsion in mice infected with T. spiralis only. T. brucei superinfection resulted in monocytosis, suppressed eosinophilia, significant decrease in PCV (p<0.001), higher numbers of adult worms (p<0.001) and failure to expel all adult worms by Day 12 post infection (p.i.). Regardless, they produced anti-Trichinella IgG(1) responses similar to those of the vaccinated non-T. brucei-infected group. T. brucei also suppressed the proliferative responses of spleen cells to stimulation with Con A and T. spiralis antigen, and induced strong production of interferon-gamma (IFN-gamma) in culture supernatants of antigen stimulated spleen and mesenteric lymph node cells. Interleukin-5 (IL-5) production was suppressed by T. brucei in supernatants of Con A- and antigen-stimulated spleen cells. It was concluded that trypanosome infections and the associated immunosuppression are of great practical significance in trypanosome endemic areas, especially with regards to disease control programmes involving vaccine-induced herd immunity.

Topics: Animals; Antibodies, Helminth; Antigens, Helminth; Concanavalin A; Cytokines; Eosinophils; Female; Hematocrit; Immune Tolerance; Lymphocyte Activation; Mice; Models, Immunological; Monocytes; Parasitemia; Protozoan Vaccines; Trichinella; Trypanosoma brucei brucei; Trypanosomiasis, African

Helminth infections are frequently massive, chronic and strong inductors of Th2-type cytokines. This implies that infection by such parasites could alter the susceptibility to subsequent infections by other pathogens, particularly intracellular parasites. We therefore explored whether a persistent infection, caused by Taenia crassiceps cysticerci, in BALB/c mice could affect susceptibility to a later infection by Trypanosoma cruzi. We found that the presence of the cysticerci indeed modified the immune response and the susceptibility to T. cruzi, and that these modifications depended on the time-course evolution of the initial infection. Coinfection with the protozoan in the early stages of the helminth infection, induced a delay on the onset of parasitaemia, early specific production of IFN-gamma and high specific production of IL-4. A significant increase in susceptibility to T. cruzi was observed only when mice were coinfected in late stages when the helminth load is greater and a Th2 type response against it is predominant. The in vitro specific response to T. cruzi antigens was then characterized by low levels of both IFN-gamma and IL-4. These findings suggest that chronic helminth infections could potentially have a significant influence over the immune response and hence susceptibility to other pathogens.

Topics: Animals; Antibody Specificity; Antigens, Helminth; Chagas Disease; Concanavalin A; Cysticercosis; Cytokines; Female; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred BALB C; Parasitemia; Spleen

The mechanisms regulating resistance or susceptibility to African trypanosomes have been enigmatic. In this study, we assessed the production of several cytokines (IL-4, IFN-gamma, and TNF-alpha) in vivo and in vitro using genetically susceptible (BALB/c) or resistant (C57BL/6) mice infected with cloned Trypanosoma congolense and the role of these cytokines in pathogenesis of this infection. Plasma of infected BALB/c mice contained higher levels of IL-4 and IFN-gamma than the plasma of infected C57BL/6 mice. Conversely, plasma TNF-alpha levels were elevated significantly in the resistant mice relative to the susceptible ones. Splenic IFN-gamma mRNA appeared earlier and were maintained at higher levels in infected BALB/c than in C57BL/6 mice. Both spontaneous and Con A-induced secretions of IL-4 and IFN-gamma by splenocytes from infected BALB/c mice were significantly higher than those from their C57BL/6 counterparts. Con A-induced proliferation of splenocytes from infected BALB/c mice was progressively suppressed. Nitric oxide was not involved in this suppression, but the suppression was positively correlated with IFN-gamma secretion. Addition of neutralizing Abs to IFN-gamma to cultures of Con A-stimulated spleen cells from infected BALB/c mice effectively reversed this suppression. Furthermore, administration of anti-IFN-gamma Abs to BALB/c mice early during infection dramatically shifted the phenotype of these susceptible mice to a more resistant-like phenotype, as expressed by a low and undulating parasitemia and a >300% increase in survival period. These results strongly suggest that the enhanced induction and secretion of IFN-gamma during T. congolense infections contribute to the relative susceptibility of BALB/c mice to the disease.

Topics: Animals; Antibodies, Monoclonal; Concanavalin A; Female; Genetic Predisposition to Disease; Immunity, Innate; Immunosuppressive Agents; Injections, Intraperitoneal; Interferon-gamma; Interleukin-10; Interleukin-4; Liver; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Parasitemia; Phenotype; RNA, Messenger; Spleen; Trypanosoma congolense; Trypanosomiasis, African; Tumor Necrosis Factor-alpha

The cardiac pathology associated with infection by Trypanosoma cruzi in mice has been suggested to be partially dependent upon cytokine responses. The pathoresistant B10.D2 mice, which display little infection-induced myocarditis, and the pathopermissive DBA/2 mice, which show significant cardiac damage, were compared for their in vitro interferon (IFN)-gamma and interleukin (IL)-4 production. Concanavalin A-stimulated spleen cells from infected B10.D2 mice produce a greater amount of IFN-gamma than DBA/2 mice, whereas the IL-4 production is only slightly greater in the B10.D2 mice than the DBA/2 mice. Parasite antigen stimulation of spleen cells from these mice results in a clearly greater IFN gamma production by the B10.D2 and a higher IL-4 level for the DBA/2 mice. The data presented suggest a relationship between an enhanced TH1-type response and decreased chronic cardiac pathogenesis, whereas a lower level of TH1 activity may play a role in cardiac involvement.

Topics: Animals; Antigens, Protozoan; Cells, Cultured; Chagas Cardiomyopathy; Chagas Disease; Concanavalin A; Disease Susceptibility; Immunity, Innate; Interferon-gamma; Interleukin-4; Mice; Mice, Inbred DBA; Mice, Inbred Strains; Parasitemia; Spleen; Th1 Cells; Th2 Cells; Trypanosoma cruzi

In this study, we describe the functional alterations in the host immune system that occur following acute infection with Plasmodium yoelii. Further, we have addressed the question whether the transient condition of altered immune responsiveness can be restored by a cytokine therapy. The lymphoproliferative response towards concanavalin A (Con A) or to cross-linked anti-CD3 mAb was significantly diminished in acutely infected mice compared to immune and normal animals. This condition was associated with poor production of IL-2. In vivo treatment with recombinant IL-2 (rIL-2) resulted in marked diminution of parasitemia (from 24% +/- 6% to 8% +/- 3%) in mice during the acute phase of infection. Despite this diminution in parasitemia, 70% of the IL-2 treated mice died by day 17 post infection. In vivo treatment with rIL-2 led to a partial but significant restoration in lymphoproliferative response to TCR-mediated (cross-linked anti-CD3 mAb) or to Con A-induced stimulation in acutely infected mice. The transcripts for IL-4, IL-5, GM-CSF, and TNF-alpha were expressed in the splenocytes from acutely infected mice not treated with rIL-2. mRNAs for IL-2, IFN-gamma, IL-6, IL-10 which were not detected in acutely infected mice could be reversed by administration of rIL-2 in vivo. We suggest that some of the hyporesponsive T-cells in the acute phase of infection have the potential to be reversed, and this reversal is manifested also at the level of cytokine gene expression.

Topics: Animals; Antilymphocyte Serum; CD3 Complex; Cell Division; Concanavalin A; Female; Gene Expression Regulation; Interferon-gamma; Interleukin-2; Malaria; Mice; Mice, Inbred BALB C; Parasitemia; Plasmodium yoelii; T-Lymphocytes