scholarly journals Treg Cells Induced by rSSP4 Derived fromT. cruziAmastigotes Increase Parasitemia in an Experimental Chagas Disease Model

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Y. Flores-García ◽  
J. L. Rosales-Encina ◽  
V. H. Rosales-García ◽  
A. R. Satoskar ◽  
P. Talamás-Rohana

Currently, there is a considerable controversy over the participation of Treg cells duringTrypanosoma cruziinfection, the main point being whether these cells play a negative or a positive role. In this work, we found that the adoptive transfer of CD4+CD25+FOXP3+T cells from rSSP4- (a recombinantTrypanosoma cruziamastigote derived protein, previously shown to have immunomodulatory properties on macrophages) immunized BALB/c donors into syngenic recipients simultaneously withT. cruzichallenge reduces cardiac inflammation and prolongs hosts’ survival but increases blood parasitemia and parasite loads in the heart. These CD4+CD25+FOXP3+Treg cells from immunized mice have a relatively TGF-β-dependent suppressive activity on CD4+T cells. Therefore, regulatory CD4+CD25+T cells play a positive role in the development of acuteT. cruziinfection by inducing immunosuppressive activity that controls early cardiac inflammation during acute Chagas disease, prolonging survival, but at the same time promoting parasite growth.

2006 ◽  
Vol 75 (2) ◽  
pp. 861-869 ◽  
Author(s):  
Joshua Kotner ◽  
Rick Tarleton

ABSTRACT Infection with the protozoan parasite Trypanosoma cruzi results in a robust and multifaceted immune response that controls parasite load but is unable to completely clear infection, resulting in parasite persistence and a chronic illness known as Chagas' disease in humans. The severity of Chagas' disease is correlated with persistent parasitism of muscle, neuronal, and gut tissues. The natural immunomodulatory function of endogenous CD4+ CD25+ regulatory T cells (Treg cells) to limit hyperactive immune responses may be exploited by microbes to persist despite host responses. In this study, we show that Treg cells are not necessary for T. cruzi evasion of immune responses during acute or chronic infection. In vivo anti-CD25 monoclonal antibody-mediated depletion of Treg cells from mice prior to challenge with a lethal strain or prior to and during acute infection with a nonlethal strain of parasite neither improved nor worsened the outcome of immune responses: differences in parasitemia, kinetics of antigen-specific CD8+ T-cell expansion, and CD8+ T-cell effector function (both in vivo and ex vivo) were of similar magnitudes for both depleted and control groups. Furthermore, depletion of CD25+ cells from chronically infected mice did not enhance immune responses of muscle-derived CD8+ T cells, nor could FoxP3 mRNA/scurfin-expressing leukocytes be isolated from muscle tissue. Based on the results of this study, it is concluded that Treg cells do not appear to play a major role in regulating CD8+ T-cell effector responses during the acute phase of infection or in the muscles of mice during chronic T. cruzi infection.


2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Marcela Hernández-Torres ◽  
Rogério Silva do Nascimento ◽  
Monica Cardozo Rebouças ◽  
Alexandra Cassado ◽  
Kely Catarine Matteucci ◽  
...  

AbstractChagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8+ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response. Interestingly, the role of Bim during infections remains largely unidentified. To explore the role of Bim in Chagas disease, we infected WT, Bim+/−, Bim−/− mice with trypomastigotes forms of the Y strain of T. cruzi. Strikingly, our data revealed that Bim−/− mice exhibit a delay in the development of parasitemia followed by a deficiency in the control of parasite load in the bloodstream and a decreased survival compared to WT and Bim+/− mice. At the peak of parasitemia, peritoneal macrophages of Bim−/− mice exhibit decreased NO production, which correlated with a decrease in the pro-inflammatory Small Peritoneal Macrophage (SPM) subset. A similar reduction in NO secretion, as well as in the pro-inflammatory cytokines IFN-γ and IL-6, was also observed in Bim−/− splenocytes. Moreover, an impaired anti-T. cruzi CD8+ T-cell response was found in Bim−/− mice at this time point. Taken together, our results suggest that these alterations may contribute to the establishment of a delayed yet enlarged parasitic load observed at day 9 after infection of Bim−/− mice and place Bim as an important protein in the control of T. cruzi infections.


2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Adriana Egui ◽  
M. Carmen Thomas ◽  
Ana Fernández-Villegas ◽  
Elena Pérez-Antón ◽  
Inmaculada Gómez ◽  
...  

ABSTRACT One of the current greatest challenges of Chagas disease is the establishment of biomarkers to assess the efficacy of drugs in a short period of time. In this context, the reactivity of sera from 66 adults with chronic indeterminate Chagas disease (IND) for a set of four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973d) was analyzed before and after benznidazole treatment. The results showed that the reactivity against these antigens decreased at 9, 24, and 48 months after treatment. Moreover, the 42.4% and 68.75% of IND patients met the established standard criteria of therapeutic efficacy (STEC) at 24 and 48 months posttreatment, respectively. Meeting the STEC implied that there was a continuous decrease in the reactivity of the patient sera against the four antigens after treatment and that there was a substantial decrease in the reactivity for at least two of the antigens. This important decrease in reactivity may be associated with a drastic reduction in the parasite load, but it is not necessarily associated with a parasitological cure. After treatment, a positive PCR result was only obtained in patients who did not meet the STEC. The percentage of granzyme B+/perforin+ CD8+ T cells was significantly higher in patients who met the STEC than in those who did not meet the STEC (35.2% versus 2.2%; P < 0.05). Furthermore, the patients who met the STEC exhibited an increased quality of the multifunctional response of the antigen-specific CD8+ T cells compared with that in the patients who did not meet the STEC.


1990 ◽  
Vol 32 (5) ◽  
pp. 379-383 ◽  
Author(s):  
Anna Maria Simonsen Stolf ◽  
Eufrosina Setsu Umezawa ◽  
Bianca Zingales

A radioactive Western-blotting technique was developed by which the reactivity of Immunoglobulins (Igs) from different classes to both membrane radiolabelled and internal parasite antigens is simultaneously identified. The method includes radioiodination of parasites, polypeptide fractionation by SDS-PAGE, Western-blot transfer and autoradiography of the immunoblots developed with anti-Igs conjugates labelled with enzymes. The analysis is then performed by the comparison of common bands on the autoradiograms and the respective substrate stained nitrocellulose blots. This technique was used to analyse T. cruzi trypomastigote surface labelled antigens reactive to IgM, IgA and IgG specific antibodies. A different pattern of reactivity with acute Chagas' disease patients sera was thus obtained.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Manuel Calvopina ◽  
Gabriela Segovia ◽  
William Cevallos ◽  
Yosselin Vicuña ◽  
Jaime A. Costales ◽  
...  

2020 ◽  
Vol 204 (6) ◽  
pp. 1571-1581
Author(s):  
Gonzalo R. Acevedo ◽  
Natalia A. Juiz ◽  
Andrea Ziblat ◽  
Lucas Pérez Perri ◽  
Magalí C. Girard ◽  
...  

2018 ◽  
Vol 12 (5) ◽  
pp. e0006480 ◽  
Author(s):  
Elena Pérez-Antón ◽  
Adriana Egui ◽  
M. Carmen Thomas ◽  
Concepción J. Puerta ◽  
John Mario González ◽  
...  

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