Innate immunity and regulatory T-cells in human Chagas disease: what must be understood?

Sathler-Avelar, Renato; Vitelli-Avelar, Danielle Marquete; Teixeira-Carvalho, Andréa; Martins‐Filho, Olindo Assis

doi:10.1590/s0074-02762009000900031

Cited by 46 publications

(46 citation statements)

References 45 publications

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“…In addition, Tregs were also implicated in the human immune response against T. cruzi. A higher frequency of circulating Tregs was found in patients with the indeterminate form in relation to the cardiac form of the disease, with the majority of CD4 + CD25 + cells expressing FoxP3 (Araújo et al 2007;Sathler-Avelar et al 2009). …”

Section: Discussionmentioning

confidence: 99%

In vivoinfection byTrypanosoma cruzi: The conserved FLY domain of the gp85/trans-sialidase family potentiates host infection

et al. 2010

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Trypanosoma cruzi is a protozoan parasite that infects vertebrates, causing in humans a pathological condition known as Chagas' disease. The infection of host cells by T. cruzi involves a vast collection of molecules, including a family of 85 kDa GPI-anchored glycoproteins belonging to the gp85/trans-sialidase superfamily, which contains a conserved cell-binding sequence (VTVXNVFLYNR) known as FLY, for short. Herein, it is shown that BALB/c mice administered with a single dose (1 μg/animal, intraperitoneally) of FLY-synthetic peptide are more susceptible to infection by T. cruzi, with increased systemic parasitaemia (2-fold) and mortality. Higher tissue parasitism was observed in bladder (7·6-fold), heart (3-fold) and small intestine (3·6-fold). Moreover, an intense inflammatory response and increment of CD4+ T cells (1·7-fold) were detected in the heart of FLY-primed and infected animals, with a 5-fold relative increase of CD4+CD25+FoxP3+ T (Treg) cells. Mice treated with anti-CD25 antibodies prior to infection, showed a decrease in parasitaemia in the FLY model employed. In conclusion, the results suggest that FLY facilitates in vivo infection by T. cruzi and concurs with other factors to improve parasite survival to such an extent that might influence the progression of pathology in Chagas' disease.

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Section: Discussionmentioning

confidence: 99%

In vivoinfection byTrypanosoma cruzi: The conserved FLY domain of the gp85/trans-sialidase family potentiates host infection

et al. 2010

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“…During this stage the macrophages induce a cascade of cytokines: initially they produce interleukin (IL)-12, which acts on NK cells to induce the production of interferon (IFN)γ, which in turn increases the production of IL-12, tumor necrosis factor (TNF)α and NO in the macrophage, thus contributing to the elimination of the parasite [27] . At the same time, both types of cells synthesize regulatory cytokines such as IL-10 and IL-4 to reduce the harmful effects associated with excess stimulation of the immune system [28] . In very early stages of the infection, components of T. cruzi, including its DNA and membrane glycoconjugates, trigger the innate response through their interaction with Toll like Receptors: TLR2, TLR4 and TLR9 in macrophages and dendritic cells.…”

Section: Soluble Mediators and Cellsmentioning

confidence: 99%

Modulation of immune response in experimental Chagas disease

Basso

2013

WJEM

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“…During the initial phases of infection, macrophages produce cytokines such as interleukin 12 and TNF-α that induce production of interferon gamma (IFN-γ). This IFN-γ, produced by CD4 + and CD8 + T-lymphocytes, is essential for the control of infection (Chessler et al, 2009;Sathler-Avelar et al, 2008;Sathler-Avelar et al, 2009;Une et al, 2003). In macrophages activated by IFN-γ, intracellular parasite growth is controlled through nitric oxide (NO) production.…”

Section: Immunologic Mechanisms For Parasite Control and Heart Damagementioning

confidence: 99%

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

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Innate immunity and regulatory T-cells in human Chagas disease: what must be understood?

Abstract: There is a general consensus that during chronic

Cited by 46 publications

References 45 publications

In vivoinfection byTrypanosoma cruzi: The conserved FLY domain of the gp85/trans-sialidase family potentiates host infection

In vivoinfection byTrypanosoma cruzi: The conserved FLY domain of the gp85/trans-sialidase family potentiates host infection

Modulation of immune response in experimental Chagas disease

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

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