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Thermal regulation of acquired immune response against Paracoccidioides brasiliensis

Grant number: 19/26164-6
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2020
Effective date (End): September 24, 2022
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher:Alexandre Alarcon Steiner
Grantee:Gabriela Carvalho Santos Ferreira
Home 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

Sepsis (systemic inflammation caused by infection) is one of the diseases that most kills in Brazil and worldwide. A change in the thermal state from fever to hypothermia is a milestone in the most severe sepsis. However, while such a phenomenon is generally seen as a sign of disorder and malignancy, recent studies indicate that such hypothermia represents a regulated response whose benefits exceed those of fever in the most severe cases of sepsis. However, the benefits of hypothermia appear to occur in the acute phase of the immune response and may be costly in developing the long-term acquired immune response. There are animal strains, such as B10.A mice, that respond to infections with robust innate immune response and inadequate acquired immune response by infection with the fungus P. brasiliensis, developing hypothermia in the first 48 hours of infection when subjected to an ambient temperature of 24ºC. Therefore, this project has the interest to study this animal model in order to evaluate if the ineffectiveness of the late/acquired immune response of B10.A mice against P. brasiliensis is due, at least in part, to the development hypothermia rather than fever within the first 48 hours of infection. To test this hypothesis, the fungus will be inoculated via the endotracheal route of mice 10 days after surgery to accommodate the temperature probe. Experiments to analyze the relationship between temperature and fungal load (CFU) and lung injury (histology), as well as their relationship with dendritic cell and T lymphocyte phenotypes, by cytometry, will be performed two and ten weeks after infection. (AU)

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