Estudo do efeito dos antígenos imunomoduladores de Phythium insidiosum em modelo murino com criptococose experimental.

Abstract

The central objective of this investigation was to test if the immunomodulatory properties of Pythium insidiosum antigens could decrease the time of treatment with amphotericin B in an animal model of Cryptococcus gattii. It had been reported that dogs, horses and humans with pythiosis, caused by P. insidiosum, developed in the infected tissues a typical Th2 response, with eosinophils, mast cells and giant cells. This inflammatory reaction switched to a Th1 subset in horses injected with P. insidiosum immunogens resulting in the cure of the infection. Soon it was evident that P. insidiosum immunogens not only had a positive impact on pythiosis cases, but also on diseases that triggered a Th2 such as: skin allergies, equine sarcoid, mastitis and others. However, the testing of its immunomodulatory properties in an animal model of pythiosis had been unsuccessful. Thus, in this study we proposed the use a C57 BL/6 mouse inoculated with C. gattii as an animal model to evaluate if the intraperitoneal injection of P. insidiosum immunogens can increase the rate of survival in the above model treated with both, amphotericin B and the immunomodulator. The collected data showed that the injected animals tolerated well the immunomodulator. Side effects related to P. insidosum immunogens were not observed. A statically significant increase in the number of phagocytic cells on mice challenged with C. gattii and then injected with amphotericin B and the immunomodulatory. This result is strongly supported by the increment in white blood cells recorded in cure cases of pythiosis in humans and lower animals. This finding is also in agreement with the significant increase observed in the intracellular proliferation index (IPR), reactive oxygen species (ROS) and the peroxynitrite levels in mice injected with the immunomodulator. The results suggest that immunomodulator as a positive impact in the innate immune system of the injected mice. Interestingly, the above data contrast with the survival rate, showing not difference between the controls and the mice injected only with the immunomodulator. Interestingly, the combination of both amphotericin B and the immunomodulator showed in culture the lowest number of colony forming units (CFU), a result that had statistical support. This finding suggests that the decrease in CFU in mice inoculated with amphotericin B in combination with immunomodulator, was possibly due to combine synergism between the antifungal and the immunomodulator. Histopathological findings