O papel do imunoproteassoma na resposta imune contra a infecção pela bactéria Brucella abortus

Abstract

The immunoproteasome is a specific proteasome isoform constituted of three subunits termed β1i, β2i and β5i. Its proteolytic activity enhances the quantity and quality of peptides to be presented by MHC class I molecules to CD8+ T cells. However, the role of combined deficiency of the three immunoproteasome subunits in protective immunity against bacterial pathogens have not been investigated. In this study, we addressed the role of immunoproteasome during Brucella abortus infection, an intracellular bacterium that requires CD8+ T cell responses for control of infection. Here, we demonstrate that immunoproteasome triple knockout mice (TKO) were more susceptible to the Brucella infection. This observed susceptibility was accompanied with reduced IFN-γ production by mouse CD4+ and CD8+ T lymphocytes. Moreover, the absence of the immunoproteasome had an impact on dendritic cells MHC-I surface expression and antigen presentation by these cells. CD8+ T cell function, which plays a pivotal role in B. abortus immunity, also presented partial impairment of granzyme-B expression and consequently reduced cytotoxic activity. In conclusion, these results strongly suggest that immunoproteasome subunits are important components in host resistance to B. abortus infection by impacting both the magnitude and quality of CD8+ T cell responses.