Cell mediated immunity in Chagas' disease: Trypanosoma cruzi antigens induce suppression of the in vitro proliferative response of mononuclear cells

Mosca, W; Briceño, Luis; Hernandez, Maria Ignacia

doi:10.1590/s0074-02761991000200002

Cited by 12 publications

(7 citation statements)

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“…Abnormalities in T lymphocyte proliferation are described in T. cruzi -infected mice [31] and in human PBMCs exposed in vitro to T. cruzi antigens [32], [33]; and have been related with decreased expression of IL-2 and IL-2R, in addition to diminished cyclin D2 phosphorylation [34]. Although, the mechanisms of proliferative dysfunction on CD8+ T cells in Chagas disease need further research, previous studies suggest that they could be related to a decreased expression of co-stimulatory molecules, γ common receptor cytokine starvation or expression of inhibitory receptors as PD-1 [11], [17].…”

Section: Discussionmentioning

confidence: 99%

T Lymphocytes from Chagasic Patients Are Activated but Lack Proliferative Capacity and Down-Regulate CD28 and CD3ζ

et al. 2013

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BackgroundChronic persistent infections have been associated with T lymphocytes functional impairment. The aim of this study was to compare the activation status, the proliferative potential and the expression of CD28 and CD3ζ chain on T lymphocytes between chronic chagasic patients and uninfected controls.Methodology/Principal FindingsForty-two chronic chagasic patients, 28 healthy individuals and 32 non-chagasic cardiomyopathy donors were included. Peripheral blood was marked for CD3, CD4, CD8, HLA-DR, CD28, CD38 and intracellular CD3ζ. Peripheral blood mononuclear cells were stained with carboxyfluorescein diacetate succinimidylester and incubated with T. cruzi lysate or phytohemagglutinin for five days. Cells from 3 healthy controls were incubated with T. cruzi trypomastigotes separated with transwells; and the expression of CD3ζ chain and proliferation index was determined. Heart-infiltrating cells from two chronic chagasic patients were tested for the aforementioned cellular markers. Chagasic patients displayed higher frequencies of CD4+/HLA-DR+/CD38+ (8.1%±6.1) and CD8+/HLA-DR+/CD38+ (19.8±8.9) T cells in comparison with healthy (1.6±1.0; 10.6±8.0) and non-chagasic cardiomyopathy donors (2.9±2.9; 5.8±6.8). Furthermore, the percentage of CD4+ activated T cells was higher in chagasic patients with cardiac involvement. CD8+ T cells proliferation index in chagasic donors (1.7±0.3) was lower when compared with healthy (2.3±0.3) and non-chagasic cardiomyopathy individuals (3.1±1.1). The frequencies of CD4+/CD28+ and CD8+/CD28+ T cells, as well as the CD3ζbright/CD3ζdim% ratios in CD4+ and CD8+ were lower in chagasic patients when compared with both control groups. The CD3ζbright/CD3ζdim% ratio and proliferative indexes for CD4+ and CD8+ T lymphocytes decreased gradually in those cells cultivated with parasites and displayed lower values than those incubated with medium alone. Finally, heart-infiltrating T cells from two T. cruzi infected patients also expressed activation markers and down-regulate CD28 and CD3ζ.ConclusionsCD8+ T lymphocytes from chagasic donors displayed reduced proliferative capacity, which might be associated with CD3ζ down-regulation and diminished CD28 expression on CD4 T cells.

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Section: Discussionmentioning

confidence: 99%

T Lymphocytes from Chagasic Patients Are Activated but Lack Proliferative Capacity and Down-Regulate CD28 and CD3ζ

et al. 2013

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“…When mice are infected with Trypanosoma brucei , their B lymphocytes arrest in G0/G1 (Sacco et al 1994), which probably accounts for the greatly reduced responsiveness of these immune cells during chronic infection of the animal with T. brucei. While many parasitic infections result in an arrest or a slowing of the cell cycle (Mosca, Briceno, and Hernandez 1991; Vassella et al 1997; Yao, Bohnet, and Jasmer 1998), this is not always the case. When a target cell is infected with Coxiella burnetti , a parasite that resides within a PV, the host cell continues to cycle.…”

Section: Discussionmentioning

confidence: 99%

“…Because the PVs become so large in these cells, cell division would have a significant, detrimental effect on the integrity of the vacuole and might impact the viability of the developing parasite stages. Since infection with other parasites has been shown to affect cell cycles in the infected host (Matthews and Gull 1994; Mosca, Briceno, and Hernandez 1991; Roman, Coriz, and Baca 1986; Vassella et al 1997), we have hypothesized that infection with Encephalitozoon blocks cell cycling by host cells.…”

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confidence: 99%

Infection by Microsporidia Disrupts the Host Cell Cycle

Scanlon

Shaw

Zhou

et al. 2000

J Eukaryotic Microbiology

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ABSTRACT. Microsporidia of the genus Encephalitozoon infect mammalian cells and have become a source of morbidity and mortality in immunocompromised humans. Encephalitozoon microsporidia develop and mature within parasitophorous vacuoles, enlarging the vacuole over time until it eventually occupies most of the cytoplasm of the host cell. The ability of the host cell to accommodate such a large burden for several days suggests that the parasite subverts normal host cell processes to ensure optimal environmental conditions for its growth and development. Since this environment would be threatened if cell division of the host cell occurred, we have formulated the hypothesis that infection with Encephalitozoon microsporidia induces an arrest in the cell cycle of the host cell. In support of this hypothesis, we have found that mitotic index and DNA duplication are reduced in infected cells as compared to uninfected cells. The number of host cell nuclei in S phase is increased. The levels of cyclin D1 and the percentage of cells in G1 are reduced; however, the levels of cyclin B1 are elevated even though the percentage of cells in G2/M is decreased. These results suggest that host cells infected with Encephalitozoon microsporidia are blocked at multiple points in the cell cycle.

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“…In patients progressing to the chronic phase, a robust expansion of T cell response to parasite and host-derived antigens has been clearly demonstrated [146,155,156,157]. A high frequency of activated T cells was found in peripheral blood of indeterminate and cardiac patients [157,158] and in inflammatory infiltrate observed in the hearts of cardiac patients [159].…”

Section: Human Immunity To T Cruzi Infectionmentioning

confidence: 99%

Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease

et al. 2012

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Chagas disease caused by Trypanosoma cruzi remains an important neglected tropical disease and a cause of significant morbidity and mortality. No longer confined to endemic areas of Latin America, it is now found in non-endemic areas due to immigration. The parasite may persist in any tissue, but in recent years there has been increased recognition of adipose tissue both as an early target of infection and a reservoir of chronic infection. The major complications of this disease are cardiomyopathy and megasyndromes involving the gastrointestinal tract. The pathogenesis of Chagas disease is complex and multifactorial involving many interactive pathways. The significance of innate immunity, including the contributions of cytokines, chemokines, reactive oxygen species, and oxidative stress, has been emphasized. The role of the components of the eicosanoid pathway such as thromboxane A2 and the lipoxins has been demonstrated to have profound effects as both pro-and anti-inflammatory factors. Additionally, we discuss the vasoconstrictive actions of thromboxane A2 and endothelin-1n Chagas disease. Human immunity to T. cruzi infection and its role in pathogen control and disease progression have not been fully investigated. However, recently, it was demonstrated that a reduction in the anti-inflammatory cytokine IL-10 was associated with clinically significant chronic chagasic cardiomyopathy.

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Cell mediated immunity in Chagas' disease: Trypanosoma cruzi antigens induce suppression of the in vitro proliferative response of mononuclear cells

Cited by 12 publications

References 0 publications

T Lymphocytes from Chagasic Patients Are Activated but Lack Proliferative Capacity and Down-Regulate CD28 and CD3ζ

T Lymphocytes from Chagasic Patients Are Activated but Lack Proliferative Capacity and Down-Regulate CD28 and CD3ζ

Infection by Microsporidia Disrupts the Host Cell Cycle

Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease

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