Modulação imunológica preventiva aplicada ao controle de infecções bacterianas por salmonella typhimurium pelo uso de lectinas

Abstract

Infectious diseases are a leading cause of death throughout the world. Among these, bacterial infections stand out due to the enormous diversity of bacteria and their evolutionary and adaptive abilities. Inappropriate inflammatory responses have been associated with these infections and despite contemporaneous scientific approaches, timely diagnosis and proper treatment of systemic bacterial infection are still a challenge for public health. Thus, this study evaluated the ability of Canavalia brasiliensis (ConBr) and Cratylia argentea (CFL) lectin in modulating systemic inflammation caused by Salmonella enterica serovar Typhimurium. The lectins were purified by affinity chromatography on Sephadex G50. Toxicology and the pharmacological security of lectins was evaluated. Both lectins exhibited no toxicity up to 2000 mg/kg. Mice were inoculated intraperitoneally with lectins (10 mg/kg) within 72, 48 and 24 h before infection with Salmonella (107 CFU/mL). Animals treated with ConBr and CFL, respectively, showed 100% and 90% survival, seven days after infection. This protocol significantly reduced the bacteria in blood, peritoneal fluid and in main organs such as liver and spleen. It was also observed a reversal of the neutrophil migration failure, leukopenia, as well as reduction of cytokine levels (TNF- α, IL- 1 and IL -10) and nitric oxide on the serum. In addition, elevated peritoneal fluid concentration of nitric oxide and increase in the number of platelets were found. In vitro analyzes identified that both lectins did not exhibit antibacterial activity, can decrease the time of activation of complement system and increase intrinsic and extrinsic clotting time. Lectins had no curative effect when administered after infection and none protective effect when inoculated either intravenously or orally. Through proteomic analysis, proteins related to infection and to modulating action of lectins were identified. According to our results, we found that lectins can act on macrophages/monocytes, controlling their activation and thereby influencing the inflammatory process, protecting the animals from septic shock. These results represent an interesting approach for the control of infections, using lectins independently or associated with antibiotics whose action is directly on microorganisms.