Evaluation of the Role of Legionella longbeachae Capsule in Immunological Modulation and Pathophysiology of Lethal Infection in Murine Models

• Grant number: 25/06480-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2025
• End date: January 31, 2030
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Pedro Henrique Medeiros Câmara
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/11342-6 - Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens, AP.TEM

Abstract

Legionella longbeachae is a Gram-negative, facultative intracellular bacterium responsible for causing a severe and atypical form of pneumonia known as Legionnaires' disease. Unlike other species of the Legionella genus, L. longbeachae is capable of establishing an infectious process in the lungs of different mouse strains, with high replication rates and mortality. Among the factors that may explain this difference in lethality between species, the presence of a polysaccharide capsule stands out. Preliminary evidence suggests that this structure participates in immune evasion, activation of neutrophil extracellular traps (NETs), and induction of tissue damage, contributing to the lethality of the infections. On the other hand, the mechanism by which the capsule triggers these processes has not yet been investigated. Based on this, the aim of this project is to investigate the role of the capsule in the pathogenicity of L. longbeachae, with emphasis on the mechanisms involved in tissue damage and pathways associated with the host immune response. In this context, the activation of NETs release pathways and the involvement of associated factors such as neutrophil elastase and type I interferon will be evaluated, in order to understand how the capsule may influence these processes. By elucidating the role of the capsule in the pathogen's virulence and in the mechanisms associated with tissue damage, this proposal aims to deepen our understanding of the host-pathogen interaction in the Legionella genus, providing relevant insights into both bacterial biology and the immune response involved. (AU)