Highly conserved CDR3 region in circulating CD4+Vβ5+ T cells may be associated with cytotoxic activity in Chagas disease

Menezes, Cristiane Alves da Silva; Sullivan, Andrew; Falta, Michael T.; Mack, Douglas G.; Freed, Brian M.; Rocha, Manoel Otávio da Costa; Gollob, Kenneth J.; Fontenot, Andrew P.; Dutra, Walderez Ornelas

doi:10.1111/j.1365-2249.2012.04608.x

Cited by 9 publications

(23 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, the different tissue tropisms were correlated with different MHC gene expression in the murine host (30). Studies with Chagas patients also suggested that some MHC alleles could be associated with clinical forms of chronic Chagas disease (31, 32). Despite these findings, it is still difficult to establish a relationship between the genetic diversity of parasite and clinical manifestation of human Chagas disease.…”

Section: Chagas Disease: a Complex Host-parasite Interaction Drives Pmentioning

confidence: 99%

Immunoregulatory networks in human Chagas disease

Dutra

Menezes

Magalhães

et al. 2014

Parasite Immunology

135

133

View full text Add to dashboard Cite

Summary Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and, thus, influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies have led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks.

show abstract

Section: Chagas Disease: a Complex Host-parasite Interaction Drives Pmentioning

confidence: 99%

Immunoregulatory networks in human Chagas disease

Dutra

Menezes

Magalhães

et al. 2014

Parasite Immunology

135

133

View full text Add to dashboard Cite

show abstract

“…In this study, we evaluated the influence of single and co‐infection with isolates belonging to DTU TcIV and TcV on the immunological characteristics of human monocytes. TcIV occurs in North and South America and is associated with human Chagas disease in Venezuela and in the Brazilian Amazon . It is speculated that TcIV parasites are responsible for the low parasitemia and morbidity seen in chronic Chagas disease in Amazonas State in Brazil, despite a high seroprevalence .…”

Section: Discussionmentioning

confidence: 99%

“…Nonexcluding hypotheses argue that T‐cell exhaustion is the cause of the severe clinical form of Chagas disease and that the balance between the inflammatory (TNF) and anti‐inflammatory (IL‐10) cytokines is crucial for the clinical outcome . Although T cells from Chagas patients can produce TNF and IL‐10, monocytes are the main source of these cytokines in Chagas disease …”

Section: Introductionmentioning

confidence: 99%

Co‐infection with distinct Trypanosoma cruzi strains induces an activated immune response in human monocytes

Magalhães

Passos

Chiari³

et al. 2019

Parasite Immunology

View full text Add to dashboard Cite

Aims The aim of the study was to evaluate the immune response triggered by the first contact of human monocytes with two T cruzi strains from distinct discrete typing units (DTUs) IV and V, and whether co‐infection with these strains leads to changes in monocyte immune profiles, which could in turn influence the subsequent infection outcome. Methods and results We evaluated the influence of in vitro single‐ and co‐infection with AM64 and 3253 strains on immunological characteristics of human monocytes. Single infection of monocytes with AM64 or 3253 induced opposing anti‐inflammatory and inflammatory responses, respectively. Co‐infection was observed in over 50% of monocytes after 15 hours of culture, but this percentage dropped ten‐fold after 72 hours. Co‐infection led to high monocyte activation and an increased percentage of both IL‐10 and TNF. The decreased percentage of co‐infected cells observed after 72 hours was associated with a decreased frequency of TNF‐expressing cells. Conclusion Our results show that the exacerbated response observed in co‐infection with immune‐polarizing strains is associated with a decreased frequency of co‐infected cells, suggesting that the activated response favours parasite control. These findings may have implications for designing new Chagas disease preventive strategies.

show abstract

“…Despite the fact that human beings have no TCR repertoire deletions compared with mice, during human Chagas disease there is also a differential expression of TCR-Vβ5 T cells from infected patients in different stages of the disease, and preferential expansion of CD4 + Vβ5 + and CD8 + Vβ5 + T cells was also observed when mononuclear cells were exposed in vitro to parasite antigens, suggesting a possible commitment of these cells in the pathology ( 113 ). The preferential expansion of Vβ5 + populations occurs in both CD28 + and CD28 − CD4 + T cell subsets and is related to restricted sequences of CDR3 ( 114 , 115 ). Interestingly, C57BL/6 mice, which do not suffer the clonal deletion of TCR-Vβ cell subsets, also expand peripherally CD8 + Vβ5 + clones during infection ( 112 ).…”

Section: The Intrathymic T-cell Repertoire and Exit Of Potentially Aumentioning

confidence: 99%

The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation

et al. 2020

View full text Add to dashboard Cite

Chagas disease, caused by the protozoan parasite T. cruzi , is a prevalent parasitic disease in Latin America. Presently, it is spreading around the world by human migration, thus representing a new global health issue. Chronically infected individuals reveal a dissimilar disease progression: while nearly 60% remain without apparent disease for life, 30% develop life-threatening pathologies, such as chronic chagasic cardiomyopathy (CCC) or megaviscerae. Inflammation driven by parasite persistence seems to be involved in the pathophysiology of the disease. However, there is also evidence of the occurrence of autoimmune events, mainly caused by molecular mimicry and bystander activation. In experimental models of disease, is well-established that T. cruzi infects the thymus and causes locally profound structural and functional alterations. The hallmark is a massive loss of CD4 + CD8 + double positive (DP) thymocytes, mainly triggered by increased levels of glucocorticoids, although other mechanisms seem to act simultaneously. Thymic epithelial cells (TEC) exhibited an increase in extracellular matrix deposition, which are related to thymocyte migratory alterations. Moreover, medullary TEC showed a decreased expression of AIRE and altered expression of microRNAs, which might be linked to a disrupted negative selection of the T-cell repertoire. Also, almost all stages of thymocyte development are altered, including an abnormal output of CD4 − CD8 − double negative (DN) and DP immature and mature cells, many of them carrying prohibited TCR-Vβ segments. Evidence has shown that DN and DP cells with an activated phenotype can be tracked in the blood of humans with chronic Chagas disease and also in the secondary lymphoid organs and heart of infected mice, raising new questions about the relevance of these populations in the pathogenesis of Chagas disease and their possible link with thymic alterations and an immunoendocrine imbalance. Here, we discuss diverse molecular mechanisms underlying thymic abnormalities occurring during T. cruzi infection and their link with CCC, which may contribute to the design of innovative strategies to control Chagas disease pathology.

show abstract

Highly conserved CDR3 region in circulating CD4+Vβ5+ T cells may be associated with cytotoxic activity in Chagas disease

Cited by 9 publications

References 37 publications

Immunoregulatory networks in human Chagas disease

Immunoregulatory networks in human Chagas disease

Co‐infection with distinct Trypanosoma cruzi strains induces an activated immune response in human monocytes

The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation

Contact Info

Product

Resources

About