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PLoS Pathog ; 20(4): e1012191, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38683845

RESUMO

An imbalance between suppressor and effector immune responses may preclude cure in chronic parasitic diseases. In the case of Trypanosoma cruzi infection, specialized regulatory Foxp3+ T (Treg) cells suppress protective type-1 effector responses. Herein, we investigated the kinetics and underlying mechanisms behind the regulation of protective parasite-specific CD8+ T cell immunity during acute T. cruzi infection. Using the DEREG mouse model, we found that Treg cells play a role during the initial stages after T. cruzi infection, restraining the magnitude of CD8+ T cell responses and parasite control. Early Treg cell depletion increased the frequencies of polyfunctional short-lived, effector T cell subsets, without affecting memory precursor cell formation or the expression of activation, exhaustion and functional markers. In addition, Treg cell depletion during early infection minimally affected the antigen-presenting cell response but it boosted CD4+ T cell responses before the development of anti-parasite effector CD8+ T cell immunity. Crucially, the absence of CD39 expression on Treg cells significantly bolstered effector parasite-specific CD8+ T cell responses, preventing increased parasite replication in T. cruzi infected mice adoptively transferred with Treg cells. Our work underscores the crucial role of Treg cells in regulating protective anti-parasite immunity and provides evidence that CD39 expression by Treg cells represents a key immunomodulatory mechanism in this infection model.


Assuntos
Antígenos CD , Apirase , Linfócitos T CD8-Positivos , Doença de Chagas , Linfócitos T Reguladores , Trypanosoma cruzi , Animais , Doença de Chagas/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T CD8-Positivos/imunologia , Camundongos , Trypanosoma cruzi/imunologia , Antígenos CD/imunologia , Antígenos CD/metabolismo , Apirase/imunologia , Apirase/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
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