Thermal modulation of the dendritic cell profile in P. brasiliensis infection

• Grant number: 19/12032-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2019
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre Alarcon Steiner
• Grantee: Lucília das Virgens Santos Souza Rodrigues
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/03418-0 - Hypothermia in Sepsis: causes and consequences, AP.TEM

Abstract

Evidence indicates that the development of hypothermia in severe forms of inflammation does not reflect thermoregulatory failure, but rather a regulated response which may have biological value, by balancing the relation between supply and demand of oxygen in the endotoxic shock and by limiting the neutrophil infiltrate in the lungs. However, such benefits short-term may have a cost in terms of developing the immune response dependent on long-term lymphocytes. In this project, this question will be evaluated in the of P. brasiliensis fungus in B10.A mice, a strain that responds to the fungus with a robust innate immune response and an acquired immune response inadequate. In preliminary experiments, we observed that the innate immune response of these animals is associated with the development of hypothermia, and that such hypothermia can be attenuated by exposure to a slightly warm environment. Such temperature dependence environment will be used to test the hypothesis that the development of hypothermia in the acute phase of infection by P. brasiliensis compromises the maturation of dendritic cells or favors the maturation of dendritic cells with tolerogenic profile. The level of maturation of the dendritic cells will be evaluated based on MHC class II expression and co-stimulatory molecules CD80 and CB86. Cells with tolerogenic profile will be identified based on the contents of indoleamine-2,3 dioxygenase and IL-27.