Severe dengue: transcription factors associated with the innate and adaptive immune response, inflammasome components and markers of programmed cell death. In situ evaluation in human lung lesions and correlations with immunopathogenic mechanisms.

• Grant number: 24/16449-1
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2025
• End date: May 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Carla Pagliari
• Grantee: Carla Pagliari
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Evandro Sobroza de Mello ; Mírian Nacagami Sotto
• Associated scholarship(s): 25/10554-0 - Signaling pathways for innate immune response against dengue virus in human lung lesions, BP.MS

Abstract

Arboviruses are associated with different known pathogens and have a major impact on Public Health, due to the risks of epidemics and dissemination. There are still no effective therapeutic measures for the control of arboviruses, and the mechanisms determining their severity are not fully understood. We consider it crucial to evaluate the participation of the innate and acquired immune response in tissue injury events and their determining factors. Considering the different arboviruses occurring in Brazil, we intend to contribute to the understanding of the pathogenesis of Dengue by analysing cases that result in death. We intend to deepen the investigations on the innate and adaptive immune response, considering the markers of anti-viral innate immunity interferon (IFN) alpha and beta, IRF2 (interferon regulatory factor 2), RIG (retinoic acid-inducible gene), STING (Stimulator of Interferon Genes) and MDA5 (melanoma differentiation associated 5), subpopulations of T and B lymphocytes, plasmacytoid dendritic cells, markers of programmed cell death (necroptosis, pyroptosis and autophagy) and inflammasome elements (NLRP1 and 3). The specimens will be analysed by systematic histological study with semi quantification or quantification of the anatomopathological events involved and characterization and immunohistochemical quantification of the mentioned markers. (AU)