<i>Trypanosoma cruzi</i>Induces Regulatory Dendritic Cells In Vitro

Poncini, Carolina Verónica; Soto, Catalina Dirney Alba; Batalla, E; Solana, María Elisa; Cappa, S. M. González

doi:10.1128/iai.01298-07

Cited by 66 publications

(88 citation statements)

References 66 publications

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“…Despite the evidence for highly effective control of T. cruzi infection in immunocompetent hosts, and the clear generation of potent parasite-specific T and B cell responses, responses to T. cruzi infection are often referred to as "suppressed" and "nonspecific" (15)(16)(17)(18). However, not surprisingly, coinfections with Listeria and T. cruzi resulted in unaltered kinetics of T cell responses to both pathogens and DC coinfected with these pathogens induce similar responses as singly infected DC.…”

Section: Discussionmentioning

confidence: 99%

“…There is no a general immunosuppressive effect of T. cruzi on CD8 ϩ T cell priming T. cruzi is often described as being generally immunosuppressive (15)(16)(17)(18). To investigate the possibility that T. cruzi infection might generally interfere with the generation of T cell responses, we coinfected either mice or DC with wild-type T. cruzi and Listeria-OVA and monitored the timing of induction of CD8 ϩ T cell response to OVA SIINFEKL and T. cruzi TSKB20.…”

Section: Parasite Burden Influences the Timing Of The Cd8 ϩ T Cell Rementioning

confidence: 99%

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Insufficient TLR Activation Contributes to the Slow Development of CD8+ T Cell Responses in Trypanosoma cruzi Infection

Padilla

Simpson

Tarleton

2009

The Journal of Immunology

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During experimental infection with Trypanosoma cruzi, mice develop a strong CD8+ T cell response focused mainly on a few immunodominant peptides encoded in trans-sialidase family genes. Despite the potency of this response, the initial emergence and peak of parasite-specific CD8+ T cells has been noted to be relatively slow. In this study, we further document this delayed onset of T cell responses to T. cruzi as measured by the increase in frequency of parasite-specific T cells, the effector function of these cells, T cell proliferation in general, and the recruitment of cells into the draining lymph nodes. This delay does not appear to be the result of general immunosuppressive effects of the infection, a limitation in parasite numbers, or parasite trafficking to lymph nodes or to the specific epitope. Increasing the initial infecting dose or the density of parasite epitopes on APCs can modestly speed the generation of anti-T. cruzi T cell responses. Given these characteristics of the response, we propose that T. cruzi is a stealth invader, largely avoiding recognition by components of the innate immune system until the infection is well established. This conclusion is supported by the ability to accelerate the induction of T cell responses to T. cruzi by administration of ligands for TLR2 and TLR9 at the time of infection. These studies highlight a previously unappreciated mechanism of immune evasion, the surreptitious establishment of infection, by the protozoan T. cruzi.

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Section: Discussionmentioning

confidence: 99%

Section: Parasite Burden Influences the Timing Of The Cd8 ϩ T Cell Rementioning

confidence: 99%

Insufficient TLR Activation Contributes to the Slow Development of CD8+ T Cell Responses in Trypanosoma cruzi Infection

Padilla

Simpson

Tarleton

2009

The Journal of Immunology

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“…cruzi appears to have evolved to manage the expression of costimulatory molecules as a strategy to persistently survive within the mammalian host. A recent study showed that the parasite is also able to exert immune evasion by downregulating CD28 ligands and major histocompatibility complex (MHC) molecules in dendritic cells (28). In addition, it has been proposed that differential expression levels of these costimulator molecules induced by the parasite can be associated with the intensity of the inflammatory response, leading to different clinical forms of the disease in humans (28,34).…”

Section: Discussionmentioning

confidence: 99%

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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“…These include macrophages, epithelial and endothelial cells, fibroblasts, dendritic cells, neurites as well as cardiomyocytes (Meyer 1942, Meyer & Xavier de Oliveira 1948, Nogueira & Cohn 19��, Henriquez et al 1981, Meirelles et al 1982a, 198�, 1999, Morris et al 1988, Schenkman et al 1988, �raujo-Jorge 1989, OrtegaBarria & Pereira 1991, �prigliano et al 199�, Procópio et al 1998, Huang et al 1999, Chuenkova & PereiHuang et al 1999, Chuenkova & PereiChuenkova & Pereira 2001, Garzoni et al 200�, Melo et al 2004, Taniwaki et al 200�, Coimbra et al 200�, Bartholomeu et al 2008, Lu et al 2008, Poncini et al 2008, Scharfstein & Lima 2008). This single variable exemplifies the multitude of host cell and parasite components that, upon interaction, lead to activation of the signalling pathways discussed below.…”

Section: Discussionmentioning

confidence: 99%

A century of research: what have we learned about the interaction of Trypanosoma cruzi with host cells?

Alves

Mortara

2009

Mem. Inst. Oswaldo Cruz

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Trypanosoma cruziInduces Regulatory Dendritic Cells In Vitro

Cited by 66 publications

References 66 publications

Insufficient TLR Activation Contributes to the Slow Development of CD8+ T Cell Responses in Trypanosoma cruzi Infection

Insufficient TLR Activation Contributes to the Slow Development of CD8+ T Cell Responses in Trypanosoma cruzi Infection

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

A century of research: what have we learned about the interaction of Trypanosoma cruzi with host cells?

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