scholarly journals Recombinant Enolase of Trypanosoma cruzi as a Novel Vaccine Candidate against Chagas Disease in a Mouse Model of Acute Infection

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Minerva Arce-Fonseca ◽  
María Cristina González-Vázquez ◽  
Olivia Rodríguez-Morales ◽  
Verónica Graullera-Rivera ◽  
Alberto Aranda-Fraustro ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Acute Infection ◽  
Parasite Burden ◽  
Protozoan Parasite ◽  
World Health ◽  
Protective Effects ◽  
Th2 Immune Response

Trypanosoma cruzi is the protozoan parasite that causes Chagas disease, which is considered by the World Health Organization to be a neglected tropical disease. Two drugs exist for the treatment of Chagas disease, nifurtimox and benznidazole; they are only effective in the acute phase, and a vaccine is currently not available. In this study, we used the recombinant enolase from T. cruzi H8 strain (MHOM/MX/1992/H8 Yucatán) (rTcENO) and its encoding DNA (pBKTcENO) to immunize mice and evaluate their protective effects in an experimental murine model of acute phase infection. Our results showed that mice vaccinated with rTcENO or its encoding DNA were able to generate typical specific antibodies (IgG1, IgG2a, and IgG2b), suggesting that a mixed Th1/Th2 immune response was induced. The parasite burden in the blood was reduced to 69.8% and 71% in mice vaccinated with rTcENO and pBKTcENO, respectively. The group vaccinated with rTcENO achieved 75% survival, in contrast to the group vaccinated with pBKTcENO that showed no survival in comparison to the control groups. Moreover, rTcENO immunization elevated the production of IFN-γ and IL-2 after the parasite challenge, suggesting that the Th1-type immune response was polarized. These results indicated that rTcENO could be used as a vaccine against Chagas disease.

scholarly journals The Blockade of Interleukin-2 During the Acute Phase of Trypanosoma cruzi Infection Reveals Its Dominant Regulatory Role

2021 ◽  
Vol 11 ◽  
Author(s):  
Jorge Nihei ◽  
Fabiola Cardillo ◽  
Jose Mengel
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells ◽  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Chagas Disease ◽  
Acute Phase ◽  
Acute Infection ◽  
Dependent Manner ◽  
Tissue Specific

Trypanosoma cruzi infection causes Chagas’ disease in humans. The infection activates the innate and adaptative immunity in an orchestrated immune response to control parasite growth, guaranteeing host survival. Despite an effective immune response to the parasite in the acute phase, the infection progresses to a chronic stage. The parasite infects different tissues such as peripheral neurons, the brain, skeletal muscle, and heart muscle, among many others. It is evident now that tissue-specific immune responses may develop along with anti-parasite immunity. Therefore, mechanisms to regulate immunity and to ensure tissue-specific tolerance are operating during the infection. Studying those immunoregulatory mechanisms is fundamental to improve host protection or control inflammatory reactions that may lead to pathology. The role of IL-2 during T. cruzi infection is not established. IL-2 production by T cells is strongly down-modulated early in the disease by unknown mechanisms and remains low during the chronic phase of the disease. IL-2 activates NK cells, CD4, and CD8 T cells and may be necessary to immunity development. Also, the expansion and maintenance of regulatory T cells require IL-2. Thus, IL-2 may be a key cytokine involved in promoting or down-regulating immune responses, probably in a dose-dependent manner. This study blocked IL-2 during the acute T. cruzi infection by using a neutralizing monoclonal antibody. The results show that parasitemia and mortality rate was lower in animals treated with anti-IL-2. The percentages and total numbers of CD4+CD25+Foxp3+ T cells diminished within three weeks of infection. The numbers of splenic activated/memory CD4 and CD8 splenic T cells increased during the acute infection. T cells producing IFN-γ, TNF-α and IL-10 also augmented in anti-IL-2-treated infected mice. The IL-2 blockade also increased the numbers of inflammatory cells in the heart and skeletal muscles and the amount of IL-17 produced by heart T cells. These results suggest that IL-2 might be involved in the immune regulatory response during the acute T. cruzi infection, dampening T cell activation through the expansion/maintenance of regulatory T cells and regulating IL-17 production. Therefore, the IL-2 pathway is an attractive target for therapeutic purposes in acute and chronic phases of Chagas’ disease.

Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation

2019 ◽  
Vol 26 (36) ◽  
pp. 6519-6543 ◽  
Author(s):  
Adriana Egui ◽  
Paola Lasso ◽  
Elena Pérez-Antón ◽  
M. Carmen Thomas ◽  
Manuel Carlos López
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cardiac Tissue ◽  
Acute Infection ◽  
Clinical Status ◽  
Chronic Phase ◽  
Parasite Load ◽  
Chronic Patients ◽  
Cruzi Infection

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.

scholarly journals Effects of betamethasone on the course of experimentai. Infection with Trypanosoma cruzi

1986 ◽  
Vol 19 (3) ◽  
pp. 161-164 ◽  
Author(s):  
Frederico G.C. Abath ◽  
Yara M. Gomes ◽  
Eridan M. Coutinho ◽  
Silvia M.L. Montenegro ◽  
Maria E.B. Melo ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Bacterial Infections ◽  
Acute Infection ◽  
Chronic Phase ◽  
Control Group ◽  
Cumulative Mortality ◽  
Histopathological Findings ◽  
Experimental Group

In this experiment, the effect of betamethasone administered in the early post- acute infection of mice by Trypanosoma cruzi was studied. This drug was administered during 30 days after the 42nd day of infection in a dose of 0.15 mg/day. The betamethasone treatment did not cause fresh outbreaks of parasitemia and the histopathological findings in the chronic phase were not different from those in the control group. The higher cumulative mortality after treatment in the experimental group was due to superimposed bacterial infections. Outbred albino mice infected with low numbers ofY strain Trypanosoma cruzi trypomastigotes were not suitable models for Chagas' disease, since after 7 months of observation only mild histological lesions developed in all the animais. Prolonged betamethasone treatment of mice infected with low numbers o/Trypanosoma cruzi of the Y strain, during the post-acute phase did not aggravate the course of infection.

Wnt Signalling Orchestrates the Immune Response and Cardiac Damage During Trypanosoma cruzi Infection

2020 ◽  
Author(s):  
Ximena Volpini ◽  
Laura Fernanda Ambrosio ◽  
Agustina Brajín ◽  
María Belen Brugo ◽  
María Pilar Aoki ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Wnt Signalling ◽  
Signalling Pathways ◽  
Chagas Cardiomyopathy ◽  
Cardiac Lesions ◽  
Parasite Replication ◽  
Chronic Chagas Disease

AbstractChagas’ cardiomyopathy is the consequence of a compromised electrical and mechanical cardiac function, with parasite persistence, unbalanced inflammation and pathological tissue remodelling, being intricately related to the myocardial aggression and the impaired function. Recent studies have shown that Wnt signalling pathways, which are important for developmental processes, play a critical role in the pathogenesis of cardiac and vascular diseases. In addition, we have reported that Trypanosoma cruzi infection activates Wnt signalling pathways in macrophages to promote their intracellular replication, with treatment of mice with IWP-L6 (an inhibitor of the O-acyl-transferase, PORCN, responsible for the post-translational modifications necessary for Wnt proteins secretion) being able to diminish parasitaemia and tissue parasitism. Therefore, Wnt signalling may contribute to the development of Chagas’ cardiomyopathy. In this work we have evaluated the effectiveness of Wnt secretion inhibition to control the parasite replication, modulate the adaptive immune response, and prevent the development of cardiac lesions in an experimental model of chronic Chagas disease. The IWP-L6 treatment, administered to T. cruzi infected BALB/c mice in a time window during the acute phase of the infection, was able to control the parasitaemia and heart parasitism together with the amelioration of the electrical, mechanical and histopathological cardiac alterations observed in chronically infected mice. Moreover, we demonstrated that during the acute phase of the infection Wnt signalling activation contributes to promote specific Th2-type immune response and to maintain the suppressive activity of Treg cells. Our data provide evidence that inhibition of Wnt signalling during the acute phase of T. cruzi infection controls the parasite replication, inhibits the development of parasite-prone and fibrosis-prone Th2-type immune response and prevents the development of cardiac lesions characteristics of chronic Chagas disease. Our study suggests that Wnt signalling pathway might be a potential target to prevent the development of T. cruzi-induced cardiomyopathy.

scholarly journals NK Cells Contribute to the Control of Trypanosoma cruzi Infection by Killing Free Parasites by Perforin-Independent Mechanisms

2004 ◽  
Vol 72 (12) ◽  
pp. 6817-6825 ◽  
Author(s):  
Thorsten Lieke ◽  
Sebastian E. B. Graefe ◽  
Ulricke Klauenberg ◽  
Bernhard Fleischer ◽  
Thomas Jacobs
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Nk Cells ◽  
Acute Phase ◽  
Initial Phase ◽  
Protozoan Parasite ◽  
Quantitative Real Time Pcr ◽  
Antiparasitic Activity ◽  
Cruzi Infection ◽  
Different Tissues

ABSTRACT The protozoan parasite Trypanosoma cruzi circulates in the blood as trypomastigotes and invades a variety of cells to multiply intracellularly as amastigotes. The acute phase leads to an immune response that restricts the proliferation of the parasite. However, parasites are able to persist in different tissues, which causes the pathology of Chagas' disease. Natural killer (NK) cells play an important role in innate resistance to a variety of pathogens. In the present study we analyzed whether NK cells participated in the control of experimental T. cruzi infection. NK cells were depleted from C57BL/6 mice by antiasialo antibodies. This treatment caused an increased parasitemia during the acute phase, but tissue parasite burdens were not significantly altered according to quantitative real-time PCR. Our results demonstrated that NK cells were activated during the initial phase of a T. cruzi infection and exhibited a contact-dependent antiparasitic activity against extracellular parasites that was independent from perforin. Thus, NK cells limit the propagation of the parasite by acting on circulating T. cruzi trypomastigotes.

scholarly journals DNA Vaccine Treatment in Dogs Experimentally Infected with Trypanosoma cruzi

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Minerva Arce-Fonseca ◽  
Ana C. Carbajal-Hernández ◽  
Mónica Lozano-Camacho ◽  
Silvia del C. Carrillo-Sánchez ◽  
Francisco-Javier Roldán ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Dna Vaccine ◽  
Stimulation Index ◽  
Therapeutic Vaccine ◽  
Heart Tissue ◽  
Th1 Response ◽  
Th2 Immune Response ◽  
And Function

Chagas disease is a chronic and potentially lethal disorder caused by the parasite Trypanosoma cruzi, and an effective treatment has not been developed for chronic Chagas disease. The objective of this study was to determine the effectiveness of a therapeutic DNA vaccine containing T. cruzi genes in dogs with experimentally induced Chagas disease through clinical, pathological, and immunological analyses. Infection of Beagle dogs with the H8 T. cruzi strain was performed intraperitoneally with 3500 metacyclic trypomastigotes/kg body weight. Two weeks after infection, plasmid DNA immunotherapy was administered thrice at 15-day intervals. The clinical (physical and cabinet studies), immunological (antibody and cytokine profiles and lymphoproliferation), and macro- and microscopic pathological findings were described. A significant increase in IgG and cell proliferation was recorded after immunotherapy, and the highest stimulation index (3.02) was observed in dogs treated with the pBCSSP4 plasmid. The second treatment with both plasmids induced an increase in IL-1, and the third treatment with the pBCSSP4 plasmid induced an increase in IL-6. The pBCSP plasmid had a good Th1 response regulated by high levels of IFN-gamma and TNF-alpha, whereas the combination of the two plasmids did not have a synergistic effect. Electrocardiographic studies registered lower abnormalities and the lowest number of individuals with abnormalities in each group treated with the therapeutic vaccine. Echocardiograms showed that the pBCSSP4 plasmid immunotherapy preserved cardiac structure and function to a greater extent and prevented cardiomegaly. The two plasmids alone controlled the infection moderately by a reduction in the inflammatory infiltrates in heart tissue. The immunotherapy was able to reduce the magnitude of cardiac lesions and modulate the cellular immune response; the pBCSP treatment showed a clear Th1 response; and pBCSSP4 induced a balanced Th1/Th2 immune response that prevented severe cardiac involvement. The pBCSSP4 plasmid had a better effect on most of the parameters evaluated in this study; therefore, this plasmid can be considered an optional treatment against Chagas disease in naturally infected dogs.

scholarly journals Electrolyzed Oxidizing Water Modulates the Immune Response in BALB/c Mice Experimentally Infected with Trypanosoma cruzi

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 974
Author(s):  
Olivia Rodríguez-Morales ◽  
Juan José Cabrera-Mata ◽  
Silvia del C. Carrillo-Sánchez ◽  
Rodolfo A. Gutiérrez-Ocejo ◽  
Lidia Baylón-Pacheco ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Acute Phase ◽  
Public Health Problem ◽  
Fold Increase ◽  
Health Condition ◽  
Major Public Health Problem ◽  
Ifn Gamma ◽  
Th2 Immune Response ◽  
General Physical

Chagas disease is a major public health problem in Latin America. The mixed Th1/Th2 immune response is required against Trypanosoma cruzi. Electrolyzed oxidizing water (EOW) has been shown to have germicidal efficacy. The objective of this study was to evaluate the EOW effectiveness in T. cruzi-infected BALB/c mice clinically, immunologically, and histologically. The severity of the infection was assessed by parasitaemia, general health condition, mortality, mega syndromes, and histological lesions. IgG, TNF-alpha, IFN-gamma, and IL-1 beta levels were quantified. The EOW administration showed a beneficial effect on parasitaemia, general physical condition, and mortality. High levels of IgG1 at 50 days postinfection were observed. Prophylactic EOW treatment was able to induce a predominantly TH1 immune response based on an IgG2a levels increase at the late acute phase, and a 10-fold increase of IFN-gamma in whole acute phase. EOW was able to control the acute phase infection as effectively as benznidazole. Splenomegaly was caused by EOW treatment and lymphadenopathy was stimulated by T. cruzi infection in all groups. Severe tissue damage was not prevented by EOW treatments. Moderate efficacy may be due to immunomodulatory properties and not to a direct toxic effect on the parasite.

scholarly journals Immune Response to Trypanosoma cruzi Shed Acute Phase Antigen in Children from an Endemic Area for Chagas' Disease in Bolivia

1997 ◽  
Vol 92 (4) ◽  
pp. 503-507 ◽  
Author(s):  
Simone Frédérique Brenière ◽  
Nina Yaksic ◽  
Jenny Telleria ◽  
Marie-France Bosseno ◽  
François Noireau ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Endemic Area

scholarly journals Early Immune Response Elicited by Different Trypanosoma cruzi Infective Stages

2021 ◽  
Vol 11 ◽  
Author(s):  
Brenda Celeste Gutierrez ◽  
Estela Lammel ◽  
Stella Maris González-Cappa ◽  
Carolina Verónica Poncini
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Cardiac Tissue ◽  
Acute Infection ◽  
Lethal Dose ◽  
Protozoan Parasite ◽  
Parasite Load ◽  
Different Populations ◽  
Antigen Presenting

Trypanosoma cruzi is a protozoan parasite that affects millions of people in Latin America. Infection occurs by vectorial transmission or by transfusion or transplacental route. Immune events occurring immediately after the parasite entrance are poorly explored. Dendritic cells (DCs) are target for the parasite immune evasion mechanisms. Recently, we have demonstrated that two different populations of DCs display variable activation after interaction with the two infective forms of the parasite: metacyclic or blood trypomastigotes (mTp or bTp) in vitro. The skin constitutes a complex network with several populations of antigen-presenting cells. Previously, we have demonstrated T. cruzi conditioning the repertoire of cells recruited into the site of infection. In the present work, we observed that mTp and bTp inoculation displayed differences in cell recruitment to the site of infection and in the activation status of APCs in draining lymph nodes and spleen during acute infection. Animals inoculated with mTp exhibited 100% of survival with no detectable parasitemia, in contrast with those injected with bTp that displayed high mortality and high parasite load. Animals infected with mTp and challenged with a lethal dose of bTp 15 days after primary infection showed no mortality and incremented DC activation in secondary lymphoid organs compared with controls injected only with bTp or non-infected mice. These animals also displayed a smaller number of amastigote nests in cardiac tissue and more CD8 T cells than mice infected with bTp. All the results suggest that both Tp infective stages induce an unequal immune response since the beginning of the infection.

scholarly journals Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

2013 ◽  
Vol 4 ◽  
Author(s):  
Juliana de Meis ◽  
Juliana Barreto de Albuquerque ◽  
Danielle Silva dos Santos ◽  
Désio Aurélio Farias-de-Oliveira ◽  
Luiz Ricardo Berbert ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Acute Infection ◽  
Mucosal Infection
Sign in / Sign up

Export Citation Format

Share Document