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Cell Death Dis ; 12(7): 692, 2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-34247195

RESUMO

Chagas disease is a life-threatening disorder caused by the protozoan parasite Trypanosoma cruzi. Parasite-specific antibodies, CD8+ T cells, as well as IFN-γ and nitric oxide (NO) are key elements of the adaptive and innate immunity against the extracellular and intracellular forms of the parasite. Bim is a potent pro-apoptotic member of the Bcl-2 family implicated in different aspects of the immune regulation, such as negative selection of self-reactive thymocytes and elimination of antigen-specific T cells at the end of an immune response. Interestingly, the role of Bim during infections remains largely unidentified. To explore the role of Bim in Chagas disease, we infected WT, Bim+/-, Bim-/- mice with trypomastigotes forms of the Y strain of T. cruzi. Strikingly, our data revealed that Bim-/- mice exhibit a delay in the development of parasitemia followed by a deficiency in the control of parasite load in the bloodstream and a decreased survival compared to WT and Bim+/- mice. At the peak of parasitemia, peritoneal macrophages of Bim-/- mice exhibit decreased NO production, which correlated with a decrease in the pro-inflammatory Small Peritoneal Macrophage (SPM) subset. A similar reduction in NO secretion, as well as in the pro-inflammatory cytokines IFN-γ and IL-6, was also observed in Bim-/- splenocytes. Moreover, an impaired anti-T. cruzi CD8+ T-cell response was found in Bim-/- mice at this time point. Taken together, our results suggest that these alterations may contribute to the establishment of a delayed yet enlarged parasitic load observed at day 9 after infection of Bim-/- mice and place Bim as an important protein in the control of T. cruzi infections.


Assuntos
Proteína 11 Semelhante a Bcl-2/deficiência , Doença de Chagas/parasitologia , Trypanosoma cruzi/patogenicidade , Animais , Proteína 11 Semelhante a Bcl-2/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/parasitologia , Células Cultivadas , Doença de Chagas/genética , Doença de Chagas/imunologia , Doença de Chagas/metabolismo , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Parasita , Interferon gama/metabolismo , Interleucina-6/metabolismo , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/parasitologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo , Carga Parasitária , Baço/imunologia , Baço/metabolismo , Baço/parasitologia , Fatores de Tempo , Trypanosoma cruzi/imunologia
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