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Understanding CD8+ T Cell Immunity to Trypanosoma cruzi and How to Improve It.

ABSTRACT: The protozoan Trypanosoma cruzi is the causative agent of Chagas' disease, endemic in Latin America but present worldwide. Research efforts have focused on the examination of immune mechanisms that mediate host protection as well as immunopathology during this parasitic infection. The study of CD8+ T cell immunity emerges as a key aspect given the critical importance of parasite-specific CD8+ T cells for host resistance throughout the infection. In recent years, new research has shed light on novel pathways that modulate the induction, maintenance, and regulation of CD8+ T cell responses to T. cruzi. This new knowledge is setting the ground for future vaccines and/or immunotherapies. Herein, we critically review and analyze the latest results published in the field.

SUBMITTER: Acosta Rodriguez EV

PROVIDER: S-EPMC6815727 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Understanding CD8+ T Cell Immunity to Trypanosoma cruzi and How to Improve It.

Acosta Rodríguez Eva V EV Araujo Furlan Cintia L CL Fiocca Vernengo Facundo F Montes Carolina L CL Gruppi Adriana A

Trends in parasitology 20191010 11

The protozoan Trypanosoma cruzi is the causative agent of Chagas' disease, endemic in Latin America but present worldwide. Research efforts have focused on the examination of immune mechanisms that mediate host protection as well as immunopathology during this parasitic infection. The study of CD8+ T cell immunity emerges as a key aspect given the critical importance of parasite-specific CD8+ T cells for host resistance throughout the infection. In recent years, new researc ...[more]

PMID: 31607632

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Project description:While it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by Trypanosoma cruzi was still poorly characterized. In order to understand the role of Treg cells during infection by this protozoan parasite, we determined in time and space the magnitude of the regulatory response and the phenotypic, functional and transcriptional features of the Treg cell population in infected mice. Contrary to the accumulation of Treg cells reported in most chronic infections in mice and humans, experimental T. cruzi infection was characterized by sustained numbers but decreased relative frequency of Treg cells. The reduction in Treg cell frequency resulted from a massive accumulation of effector immune cells, and inversely correlated with the magnitude of the effector immune response as well as with emergence of acute immunopathology. In order to understand the causes underlying the marked reduction in Treg cell frequency, we evaluated the dynamics of the Treg cell population and found a low proliferation rate and limited accrual of peripheral Treg cells during infection. We also observed that Treg cells became activated and acquired a phenotypic and transcriptional profile consistent with suppression of type 1 inflammatory responses. To assess the biological relevance of the relative reduction in Treg cells frequency observed during T. cruzi infection, we transferred in vitro differentiated Treg cells at early moments, when the deregulation of the ratio between regulatory and conventional T cells becomes significant. Intravenous injection of Treg cells dampened parasite-specific CD8+ T cell immunity and affected parasite control in blood and tissues. Altogether, our results show that limited Treg cell response during the acute phase of T. cruzi infection enables the emergence of protective anti-parasite CD8+ T cell immunity and critically influences host resistance.

Dataset Information

Understanding CD8+ T Cell Immunity to Trypanosoma cruzi and How to Improve It.

Publications

Understanding CD8<sup>+</sup> T Cell Immunity to Trypanosoma cruzi and How to Improve It.

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