Depletion of regulatory T cells decreases cardiac parasitosis and inflammation in experimental Chagas disease

Bonney, Kevin M.; Taylor, Joann M.; Thorp, Edward B.; Epting, Conrad L.; Engman, David M.

doi:10.1007/s00436-014-4300-3

Cited by 22 publications

(21 citation statements)

References 82 publications

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“…Although several studies have shown the involvement of Treg cells in CD [ 28 – 30 ], the role of Tregs in CD treatment is poorly understood, mainly in the acute phase of the infection with distinct strains. In the acute phase, Tregs probably help to decrease parasitemia and balance inflammatory response [ 56 , 63 ]. Understanding the role of Tregs could help to control the inflammatory response and tissue damage, to reduce the intense Th17 response and autoimune response observed in several infections [ 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

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Benznidazole affects expression of Th1, Th17 and Treg cytokines during acute experimental Trypanosoma cruzi infection

Gatto

Oliveira

Dias

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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BackgroundThe present study evaluated the effect of treatment with benznidazole on mRNA expression of IFN-γ, IL-17, IL-10, TGF-β and FoxP3 in spleen and heart tissue of BALB/c mice in the acute phase of an experimental infection with Trypanosoma cruzi, strains JLP or Y.MethodsThe mRNA expression of cytokines and parasite load were assessed by q-PCR. Dependent groups were compared using Student’s paired t-test and independent groups were compared using Student’s unpaired t-test.ResultsInfection with the JLP or Y strains increased expression of IFN-γ in the heart and of IL-10 and IL-17 in the spleen and heart compared to uninfected animals. Treatment increased the expression of IFN-γ and decreased the expression of IL-17, IL-10, TGF- β and Foxp3 in spleen and heart tissue compared to untreated infected animals.ConclusionBenznidazole can induce Th1 profile in the initial of the acute phase. The treatment decreased the parasite load in both organs, although the number of parasites in Y-strain-infected mice remained high. The data suggest that benznidazole may modulate cytokine expression in infection and can be dependent of the strain. However, treatment was not fully effective in the infection provoked by Y strain, probably due to the characteristics of the strain itself.

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Section: Discussionmentioning

confidence: 99%

“…Our study showed that T. cruzi infection resulted in increased IL-10, TGF-beta and Foxp3 expression compared to controls. These results suggest that both strains of T. cruzi can induce Treg and cytokine production associated with this cells [ 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

Benznidazole affects expression of Th1, Th17 and Treg cytokines during acute experimental Trypanosoma cruzi infection

Gatto

Oliveira

Dias

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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“…T regs play a preponderant role in controlling the immune response in other parasitic infections. In fact, depleting these cells decreases the number of parasites in Chagas’ disease . A number of studies describe some mechanisms for T reg suppressive actions and their effect in parasitic diseases.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 10 and dendritic cells are the main suppression mediators of regulatory T cells in human neurocysticercosis

Arce-Sillas

Álvarez-Luquín

Cárdenas

et al. 2015

Clinical and Experimental Immunology

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SummaryNeurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. It is considered that, during co-evolution, the parasite developed strategies to modulate the host's immune response. The action mechanisms of regulatory T cells in controlling the immune response in neurocysticercosis are studied in this work. Higher blood levels of regulatory T cells with CD4 with respect to controls. Interestingly, regulatory T cells express higher levels of cytotoxic T lymphocyte antigen 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor (GITR), suggesting a cell-to-cell contact mechanism with dendritic cells. Furthermore, higher IL-10 and regulatory T cell type 1 (Tr1) levels were found in neurocysticercosis patients' peripheral blood, suggesting that the action mechanism of regulatory T cells involves the release of immunomodulatory cytokines. No evidence was found of the regulatory T cell role in inhibiting the proliferative response. Suppressive regulatory T cells from neurocysticercosis patients correlated negatively with late activated lymphocytes (CD4). Our results suggest that, during neurocysticercosis, regulatory T cells could control the immune response, probably by a cell-to-cell contact with dendritic cells and interleukin (IL)-10 release by Tr1, to create an immunomodulatory environment that may favour the development of T. solium cysticerci and their permanence in the central nervous system.

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“…Indeed, deficient signaling of IL-10 correlated with increased mortality in experimental T. cruzi infection due to overwhelming inflammatory responses mediated by TNF and IFNγ ( 21 , 22 ). Depletion of Treg cells in T. cruzi -infected mice leads to reduced cardiac parasitosis and inflammation, accompanied by an augmented Th1 response early in the course of infection followed by a downregulation of this response and increased Th17 response late in infection ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi

et al. 2017

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Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice) infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able to regulate TNF-producing CD4+ T cells since their absence favor the increase of the number of TNF+ CD4+ in T. cruzi-infected mice.

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Depletion of regulatory T cells decreases cardiac parasitosis and inflammation in experimental Chagas disease

Cited by 22 publications

References 82 publications

Benznidazole affects expression of Th1, Th17 and Treg cytokines during acute experimental Trypanosoma cruzi infection

Benznidazole affects expression of Th1, Th17 and Treg cytokines during acute experimental Trypanosoma cruzi infection

Interleukin 10 and dendritic cells are the main suppression mediators of regulatory T cells in human neurocysticercosis

Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi

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