Exploring the parasite load and molecular diversity of Trypanosoma cruzi in patients with chronic Chagas disease from different regions of Brazil

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.

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Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection

Cell Death and Disease ◽

10.1038/s41419-021-03964-6 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Marcela Hernández-Torres ◽

Rogério Silva do Nascimento ◽

Monica Cardozo Rebouças ◽

Alexandra Cassado ◽

Kely Catarine Matteucci ◽

...

Keyword(s):

T Cells ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Parasite Load ◽

Peritoneal Macrophages ◽

T Cell Response ◽

No Production ◽

Similar Reduction ◽

Ifn Γ

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.

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Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: Correlation between antibody titers and development of cardiac disease severity

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0005796 ◽

2017 ◽

Vol 11 (7) ◽

pp. e0005796 ◽

Cited By ~ 8

Author(s):

Ingebourg Georg ◽

Alejandro Marcel Hasslocher-Moreno ◽

Sergio Salles Xavier ◽

Marcelo Teixeira de Holanda ◽

Eric Henrique Roma ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Disease Severity ◽

Chagas Disease ◽

Antibody Production ◽

Cardiac Disease ◽

Antibody Titers ◽

Chronic Chagas Disease

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Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for chronic Chagas disease

Memórias do Instituto Oswaldo Cruz ◽

10.1590/0074-02760140386 ◽

2015 ◽

Vol 110 (3) ◽

pp. 414-421 ◽

Cited By ~ 14

Author(s):

María Cecilia Albareda ◽

Susana Adriana Laucella

Keyword(s):

T Cell ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

T Cell Responses ◽

Cell Responses ◽

Chronic Chagas Disease

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Immunoblot assay using excreted-secreted antigens of Trypanosoma cruzi in serodiagnosis of congenital, acute, and chronic Chagas' disease.

Journal of Clinical Microbiology ◽

10.1128/jcm.34.9.2143-2147.1996 ◽

1996 ◽

Vol 34 (9) ◽

pp. 2143-2147 ◽

Cited By ~ 128

Author(s):

E S Umezawa ◽

M S Nascimento ◽

N Kesper ◽

J R Coura ◽

J Borges-Pereira ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Immunoblot Assay ◽

Chronic Chagas Disease ◽

Secreted Antigens

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A Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02436-18 ◽

2019 ◽

Vol 63 (10) ◽

Cited By ~ 4

Author(s):

Adriana Egui ◽

M. Carmen Thomas ◽

Ana Fernández-Villegas ◽

Elena Pérez-Antón ◽

Inmaculada Gómez ◽

...

Keyword(s):

T Cells ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Parasite Load ◽

Drastic Reduction ◽

Content Type ◽

Short Period ◽

Before And After ◽

Cruzi Infection

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.

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