Absence of Bim sensitizes mice to experimental Trypanosoma cruzi infection

• Published in: Cell death & disease Vol. 12; no. 7; p. 692
• Main Authors: Hernández-Torres, Marcela, Silva do Nascimento, Rogério, Rebouças, Monica Cardozo, Cassado, Alexandra, Matteucci, Kely Catarine, D’Império-Lima, Maria Regina, Vasconcelos, José Ronnie C., Bortoluci, Karina R., Alvarez, José Maria, Amarante-Mendes, Gustavo P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.07.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/106; 13/21; 13/31; 631/250/1933; 631/250/255; 64/60; Animals; Antibodies; Apoptosis; Bcl-2 protein; Bcl-2-Like Protein 11 - deficiency; Bcl-2-Like Protein 11 - genetics; BIM protein; Biochemistry; Biomedical and Life Sciences; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - parasitology; Cell Biology; Cell Culture; Cells, Cultured; Chagas disease; Chagas Disease - genetics; Chagas Disease - immunology; Chagas Disease - metabolism; Chagas Disease - parasitology; Clonal selection; Disease Models, Animal; Female; Host-Parasite Interactions; Immunology; Immunoregulation; Inflammation; Innate immunity; Interferon-gamma - metabolism; Interleukin 6; Interleukin-6 - metabolism; Life Sciences; Lymphocytes T; Macrophages; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - parasitology; Mice; Mice, Inbred C57BL; Mice, Knockout; Negative selection; Nitric oxide; Nitric Oxide - metabolism; Parasite Load; Parasitemia; Parasites; Peritoneum; Protozoa; Spleen - immunology; Spleen - metabolism; Spleen - parasitology; Splenocytes; Thymocytes; Time Factors; Trypanosoma cruzi; Trypanosoma cruzi - immunology; Trypanosoma cruzi - pathogenicity; Trypomastigotes; γ-Interferon
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-03964-6

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.