Autotransplante de baço e reatividade imunológica para o controle da infecção por Staphylococcus aureus

Abstract

Splenectomy results in greater risk of sepsis. However, its effects on the immune response and in the resistance to bacterial infections are still not well known. In this work, the capacity of mice subjected to splenectomy and autogenous transplant of the spleen for controlling Staphylococcus aureus infection was investigated. Parameters of cellular and humoral immune response connected with resistance to the infection, such as the influx of inflammatory cells to infection sites, the production of cytokines and of nitric oxide (NO), as well as the serum levels of specific antibodies were evaluated. BALB/c mice were divided into three groups: a splenectomized group (SP), a group splenectomized and autotransplanted in the retroperitoneum (AT), and a control group operated and not splenectomized (CT). Thirty days after the surgery, the mice were intravenously infected with 5x106 colony forming units (CFU) of S. aureus. Six days after the infection, samples of the plasma, serum, spleen, liver and lungs were collected. Animals of the SP group presented a higher number of bacteria in the liver and in the lungs when compared with the CT and AT groups (p < 0.05). Mice of the AT and SP groups presented a larger area of inflammation in the lungs in comparison to the CT group (p < 0.05), having higher detection of CD25+ cells and of CD40+ cells in the SP group, and greater frequency of cells CD19+ in the AT group. The analysis by flow cytometry and the evaluation of the activities of mieloperoxidase and N-acetilglicosaminidase confirmed the incident of greater influx of neutrophils and macrophages to the lungs of the mice in the SP group when compared with the CT and AT groups, and higher percentage of B cells in the lungs of mice from the AT group when compared with the CT and SP groups. The responses in the liver and in the spleen were similar in the CT and AT groups, with larger number of granulomas and higher percentage of neutrophils in the CT and AT mice in comparison to the SP group. The percentages of B cells (CD19+), T cells (CD3+), macrophages (CD4+, CD40+ and CD3-) and neutrophils (CD11b+ and CD69+) were similar in the spleens of mice from the CT and AT groups. These data suggest that the development of the immune response in the spleen can, in part, influence the response to S. aureus in the liver, favoring infection control in this organ. The profile of the production of cytokines, NO and anti-S. aureus antibodies in the mice of the SP group suggests an alteration of the immune response after the infection. The lungs of these animals showed low production of IFN-g, TNF-a and NO associated with high production of IL-10. The liver showed high production of TNF-a and low production of IFN-g, IL-1a and NO. The plasma showed low levels of IFN-g and IL-1a and high levels of TNF-a and IL-10 and the serum showed reduced levels of specific antibodies of the classes IgM and IgG1. Together, these data supply evidence that splenectomy reduces the capacity of control of the infection for S. aureus, altering the profile of immunoregulatory molecules and effector molecules in the blood stream, in the lungs and in the liver. These alterations in the humoral and cellular immune response are, in part, reversed with the performance of the autogenous spleen transplant.