Experimental autoimmune encephalomyelitis can be prevented and cured by infection with Trypanosoma cruzi

Tadokoro, Carlos E.; Vallochi, Adriana Lima; Rios, Lı́lia S.; Martins, Gislâine A.; Schlesinger, David H.; Mosca, Tainá; Kuchroo, Vijay K.; Rizzo, Luiz Vicente; Abrahamsohn, Ises A.

doi:10.1016/j.jaut.2004.05.003

Cited by 33 publications

(25 citation statements)

References 54 publications

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“…The regulatory role of T. cruzi has been previously reported in an in vivo study (53), where it was shown that experimental autoimmune encephalomyelitis is prevented and cured by infection with T. cruzi. A regulatory profile induced by T. cruzi may limit DC capacity to initiate a strong protective response, affecting the first-line mechanisms involved in the control of parasite burden and finally resulting in a failure to control the infection during acute Chagas' disease.…”

Section: Discussionmentioning

confidence: 70%

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Trypanosoma cruziInduces Regulatory Dendritic Cells In Vitro

et al. 2008

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Section: Discussionmentioning

confidence: 70%

“…Several reports showed that T. cruzi induces both Th1-type response and nonspecific immunosuppression during the acute phase of the infection (2,38,51,53). However, the mechanisms that control parasite replication and maintain low but persistent numbers of circulating parasites during the chronic phase are not well understood (25).…”

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confidence: 99%

Trypanosoma cruziInduces Regulatory Dendritic Cells In Vitro

et al. 2008

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“…Recently, growing evidence indicates that concomitant parasitic infections can reduce disease severity in different models of human autoimmune diseases (Tadokoro et al, 2004;Stevenson and Zavala, 2006;Walsh et al, 2009;Farias et al, 2011). For example, regulatory mechanisms induced during Plasmodium infection ameliorate the clinical course and immune responses of EAE (Farias et al, 2011) and co-infection with Trypanosoma species interferes with the development of EAE through a modulatory effect exerted by IL-10 that limits Th1 cells expansion (Tadokoro et al, 2004). Several models explaining this phenomenon have been proposed, including a shift from a Th1 to a Th2 T cell response (Yazdanbakhsh et al, 2001;Mohrs et al, 2005) as well as the induction of regulatory FoxP3+ T cells (Wilson et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…For example, Plasmodium infection has shown to interfere with the EAE autoimmune response through the activation of Tregs (Farias et al, 2011). Similarly, infections with Trypanosoma can confer protection against autoimmunity in arthritis models (De Trez et al, 2015) and markedly suppress the clinical course of experimental EAE, likely due to a modulatory effect of IL-10 on Th1 expansion (Tadokoro et al, 2004). Moreover, certain parasites have been found to have the ability to skew the host's response towards a Th2 phenotype, characterized by increased expression of IL-4, IL-5 and IL-13 (Mohrs et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Puentes

Dickhaut

Hofstätter

et al. 2016

J Neuroimmune Pharmacol

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Parasite proteins containing repeats are essential invasion ligands, important for their ability to evade the host immune system and to induce immunosuppression. Here, the intrinsic suppressive potential of repetitive structures within parasite proteins was exploited to induce immunomodulation in order to establish self-tolerance in an animal model of autoimmune neurological disease.We tested the tolerogenic potential of fusion proteins containing repeat sequences of parasites linked to self-antigens. The fusion constructs consist of a recombinant protein containing repeat sequences derived from the S-antigen protein (SAg) of Plasmodium falciparum linked to a CD4 T cell epitope of myelin. They were tested for their efficacy to control the development of experimental autoimmune encephalomyelitis (EAE), In addition, we used the DO11.10 transgenic mouse model to study the immune mechanisms involved in tolerance induced by SAg fusion proteins.We found that repeated sequences of P. falciparum SAg protein linked to self-epitopes markedly protected mice from EAE. These fusion constructs were powerful tolerizing agents not only in a preventive setting but also in the treatment of ongoing disease. The tolerogenic effect was shown to be antigen-specific and strongly dependent on the physical linkage of the T cell epitope to the parasite structure and on the action of anti-inflammatory cytokines like IL-10 and TGF-β. Other mechanisms include down-regulation of TNF-α accompanied by increased numbers of FoxP3 + cells. This study describes the use of repetitive structures from parasites linked to defined T cell epitopes as an effective method to induce antigen-specific tolerance with potential applicability for the treatment and prevention of autoimmune diseases.

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“…By manipulating Treg functions, parasites can turn off exacerbated and misleading immune responses against self antigens which compromise both the host and parasite survival. An example of another protozoan parasite is Trypanosoma cruzi, which can completely suppress the development of Experimental Autoimmune Encephalomyelitis (EAE) and even suppress an ongoing EAE [28]. Thus, if as conjectured, sporozoites injection can only trigger an early activation of skin Tregs, they may contribute to the survival of the host until its life cycle is complete.…”

Section: Discussionmentioning

confidence: 99%

Early skin immunological disturbance after Plasmodium-infected mosquito bites

Silva

Caetano

Monteiro

et al. 2012

Cellular Immunology

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a b s t r a c tAlthough the role of regulatory T cells (Tregs) during malaria infection has been studied extensively, such studies have focused exclusively on the role of Treg during the blood stage of infection; little is known about the detailed mechanisms of Tregs and sporozoite deposition in the dermis by mosquito bites. In this paper we show that sporozoites introduced into the skin by mosquito bites increase the mobility of skin Tregs and dendritic cells (DCs). We also show differences in MHC class II and/or CD86 expression on skin-resident dendritic cell subtypes and macrophages. From the observed decrease of the number of APCs into draining lymph nodes, suppression of CD28 expression in conventional CD4 T cells, and a low homeostatic proliferation of skin-migrated CD4 T found in nude mice indicate that Tregs may play a fundamental role during the initial phase of malaria parasite inoculation into the mammalian host.

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Experimental autoimmune encephalomyelitis can be prevented and cured by infection with Trypanosoma cruzi

Cited by 33 publications

References 54 publications

Trypanosoma cruziInduces Regulatory Dendritic Cells In Vitro

Trypanosoma cruziInduces Regulatory Dendritic Cells In Vitro

Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens

Early skin immunological disturbance after Plasmodium-infected mosquito bites

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