Avaliação dos mecanismos imunológicos envolvidos na imunomodulação induzida pela bactéria Brucella Abortus

Abstract

Brucella abortus is a Gram-negative and facultative intracellular bacterium, responsible for brucellosis in humans and animals. The immune response against this pathogen involves different mechanisms from innate and acquired immunity, including IFN-, a typical cytokine from TH1 profile, as well as CD8+ T-cells. Aside from the classic immune responses induced during an infection caused by a pathogen, the immunoregulatory pathways of the host can also be activated, limiting the range and the response time of immune responses, preventing an excessive immunopathology. Data from the literature shows the role of a range of cells and cytokines in establishing this immunoregulation such as T- and B-cell regulators and IL-10 and TGF- cytokines. Survival to an infection process therefore requires the generation of a controlled immune response. Despite the importance of immunoregulation, a diversity of pathogens have shown the capacity to stimulate some regulation mechanisms to evade the immune system and then establish the infection. In this way, the investigation of the immunoregulation processes that occur in response to the infection or are induced by the pathogenic agent become important, as these can provide information about new therapeutic approaches for the control of infections. In this context, this study aimed to evaluate the immunological mechanisms involved in the immunomodulation induced by B. abortus, in a mouse model. C57BL/6 animals were infected with B. abortus and sacrificed after one, three and six weeks of infection. Non-infected animals were used as a control group. Bacterial load was evaluated in the spleen and the cellular proliferation index was evaluated for infected and non-infected animals using the MTT method and flow cytometry. Cytokine levels (IFN-e IL-10) were evaluated through ELISA and regulatory profiles of T-cells and B-cells were assessed by flow cytometry in the splenocytes of these animals. The influence of B. abortus infection was also evaluated using a experimental autoimmune encephalomyelitis (EAE) model. As results, a decrease in cellular proliferation was observed in infected animals, with a more prominent effect in TCD8+ lymphocytes and NK (natural killer) cells. An increase in IL-10 levels was concomitantly observed. Infected animals presented a higher number of T- cells (CD4+CD25+FoxP3+ and CD8+CD25+FoxP3+) and B-cells (CD19+IL-10+) with a regulatory profile, especially after the third week of infection. Regarding EAE, an unexpected increase in clinical score was observed in infected animals when compared to control group. Thus, we concluded that Brucella abortus infection is able to induce immunoregulatory elements, although it is insufficient to cause an improvement in EAE.