The involvement of CD4+CD25+ T cells in the acute phase of Trypanosoma cruzi infection

Mariano, Flávia S.; Gutierrez, Fredy R. S.; Pavanelli, Wander Rogério; Milanezi, Cristiane M.; Cavassani, Karen A.; Moreira, Ana Paula; Ferreira, Beatriz Rossetti; Cunha, Fernando; Cardoso, Cristina Ribeiro de Barros; Silva, João

doi:10.1016/j.micinf.2008.04.009

Cited by 92 publications

(102 citation statements)

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“…Mast cells express a high density of T1/ST2 (23) and are normally associated with proinflammatory functions (29). However, in the present system, mast cells play an important anti-inflammatory role in protecting mice against CVB5-induced inflammatory pancreatitis, as indicated by enhanced pancreatitis after mast cell inhibition.…”

Section: Discussionmentioning

confidence: 66%

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The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

Sesti-Costa

Silva

Proença-Modena

et al. 2013

The Journal of Immunology

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Coxsackievirus B (CVB) is a common cause of acute and chronic infectious myocarditis and pancreatitis. Th1 cells producing IFN-γ and TNF-α are important for CVB clearance, but they are also associated with the pathogenesis of inflammatory lesions, suggesting that the modulation of Th1 and Th2 balance is likely important in controlling CVB-induced pancreatitis. We investigated the role of IL-33, which is an important recently discovered cytokine for induction of Th2-associated responses, in experimental CVB5 infection. We found that mice deficient in IL-33R, T1/ST2, significantly developed more severe pancreatitis, had greater weight loss, and contained higher viral load compared with wild-type (WT) mice when infected with CVB5. Conversely, WT mice treated with rIL-33 developed significantly lower viral titers, and pancreatitis was attenuated. Mechanistic studies demonstrated that IL-33 enhances the degranulation and production of IFN-γ and TNF-α by CD8+ T and NK cells, which is associated with viral clearance. Furthermore, IL-33 triggers the production of IL-4 from mast cells, which results in enhanced differentiation of M2 macrophages and regulatory T cells, leading to the attenuation of inflammatory pancreatitis. Adoptively transferred mast cells or M2 macrophages reversed the heightened pancreatitis in the T1/ST2−/− mice. In contrast, inhibition of regulatory T cells exacerbated the disease in WT mice. Together, our findings reveal an unrecognized IL-33/ST2 functional pathway and a key mechanism for CVB5-induced pancreatitis. These data further suggest a novel approach in treating virus-induced pancreatitis, which is a major medical condition with unmet clinical needs.

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Section: Discussionmentioning

confidence: 66%

“…injection of 100 mg/kg cromolyn sodium (Sigma Aldrich) in PBS twice a day (22). The anti-glucocorticoid-induced TNF receptor (GITR) Ab was obtained from hybridomas (DTA-1) as previously described (23). The mice were injected i.p.…”

Section: Treatment Of Mice and Cell Transfermentioning

confidence: 99%

The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

Sesti-Costa

Silva

Proença-Modena

et al. 2013

The Journal of Immunology

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“…It is mediated by cellular and soluble components of the immune response, which is poorly regulated by classic immune regulatory mechanisms. For instance, regulatory cells do not play a strong role in the modulation of this inflammatory response (17,20). Our data demonstrate that PD-1 is crucial to reduce the intensity of myocarditis.…”

Section: Discussionmentioning

confidence: 76%

Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor 1

et al. 2011

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Trypanosoma cruzi infection causes intense myocarditis, leading to cardiomyopathy and severe cardiac dysfunction. Protective adaptive immunity depends on balanced signaling through a T cell receptor and coreceptors expressed on the T cell surface. Such coreceptors can trigger stimulatory or inhibitory signals after binding to their ligands in antigen-presenting cells (APC). T. cruzi modulates the expression of coreceptors in lymphocytes after infection. Deregulated inflammation may be due to unbalanced expression of these molecules. Programmed death cell receptor 1 (PD-1) is a negative T cell coreceptor that has been associated with T cell anergy or exhaustion and persistent intracellular infections. We aimed to study the role of PD-1 during T. cruzi-induced acute myocarditis in mice. Cytometry assays showed that PD-1 and its ligands are strongly upregulated in lymphocytes and APC in response to T. cruzi infection in vivo and in vitro. Lymphocytes infiltrating the myocardium exhibited high levels of expression of these molecules. An increased cardiac inflammatory response was found in mice treated with blocking antibodies against PD-1, PD-L1, and to a lesser extent, PD-L2, compared to that found in mice treated with rat IgG. Similar results in PD-1 ؊/؊ mice were obtained. Moreover, the PD-1 blockade/deficiency led to reduced parasitemia and tissue parasitism but increased mortality. These results suggest the participation of a PD-1 signaling pathway in the control of acute myocarditis induced by T. cruzi and provide additional insight into the regulatory mechanisms in the pathogenesis of Chagas' disease.Chagas' disease is the most important cause of acquired cardiomyopathy in Latin America and is one of the outcomes resulting from the interaction between the human immune system and the hemoflagellate prokaryote Trypanosoma cruzi. In the natural infection, the flagellated forms in the feces of infected hematophagous insects of the Triatominae subfamily invade the host through skin lesions or intact mucosa. The parasite then proliferates intracellularly and disseminates systemically from the site of inoculation, causing an inflammatory reaction of variable intensity, along with splenomegaly, cardiac parasitism, and myocarditis, which is largely associated with morbidity. More frequently, a chronic asymptomatic infection is established, which eventually leads to dilated cardiomyopathy and heart failure as well as esophageal or intestinal dilatations due to the combined effects of parasite persistence, immune deregulation, autonomic denervation, and microvascular damages (21,30).The immunological mechanisms underlying this silent, relentless infection and heart pathology remain elusive despite several decades of research. It is known that T cell-mediated immune responses are essential to control the parasite replication during the acute phase of the infection (33). The cytokines gamma interferon (IFN-␥), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-␣) strengthen the activation of innate and adaptive ...

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“…In other words, collateral tissue damage in muscle tissues might be minimised if the activity of Tc1 is subjected to tight temporal control. More recently, studies by Mariano et al (2008) showed that regulatory T (CD4 + CD25 + GITR + Foxp3 + ) cells migrate into the heart of infected mice. Notably, these authors showed that treatment with anti-CD25 or anti-GITR resulted in increased mortality, while only anti-GITR enhanced tissue parasitism and inflammation, leading to increased frequencies of intracardiac CD4 + , CD8 + and CCR5…”

Section: Ts Antigens Provide Dominant Epitopes For Effector Cd8 + T Cmentioning

confidence: 99%

Back to the future in Chagas disease: from animal models to patient cohort studies, progress in immunopathogenesis research

Scharfstein

Gomes

Correa-Oliveira

2009

Mem. Inst. Oswaldo Cruz

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The involvement of CD4+CD25+ T cells in the acute phase of Trypanosoma cruzi infection

Cited by 92 publications

References 29 publications

The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor 1

Back to the future in Chagas disease: from animal models to patient cohort studies, progress in immunopathogenesis research

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