Role of NLRC4 and NRLP3 inflammasomes in the evolution of cryptococcosis induced by Cryptococcus gattii in a murine model.

• Grant number: 23/12852-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: November 30, 2024
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Rodrigo Augusto da Silva
• Grantee: Arila Adorno Scorzafava Gonçalves
• Host Institution: Vice-Reitoria de Pesquisa e Pós-Graduação. Universidade Paulista (UNIP). São Paulo , SP, Brazil

Abstract

Cryptococcus gattii is a human pathogenic fungus that can infect both immunocompromised and immunocompetent patients. It is characterized by developing severe lung diseases with low and high capacity for production of pro-inflammatory cytokines. In humans, the infection occurs after inhalation of propagules of the microorganism, normally associated with feces from pigeons and other infected birds, initially reaching the respiratory system and may disseminate and reach the Central Nervous System (CNS) mainly due to the capacity for neurological tropism. The species C. gattii is more common in tropical and subtropical areas, presenting endemic behavior in the North and Northeast regions of Brazil. Several studies support the hypothesis that the activation of inflammatory cytokines by the NLRC4 inflammasome, as part of the innate immune response, contributes to lung protection by enhancing the phagocytic capacity of macrophages and inhibiting intracellular parasitism of cryptococci. However, there are several gaps regarding the involvement of NLRC4 and NRLP3 inflammasomes during the development of cryptococcal infection, especially in the CNS. Therefore, this project aims to use an in vivo model of cryptococcal infection to better understand how the evolution of pulmonary infection by Cryptococcus gattii could be related to neurological changes resulting from neuroinflammation.