Influence of galectina-3 on the course of infection by Cryptococcus neoformans

Author(s)

Caroline Patini de Rezende

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2019-05-23

Examining board members

Fausto Bruno dos Reis Almeida; Rosymar Coutinho de Lucas; Fernanda Patrícia Gullo Luzente; Nilce Maria Martinez Rossi

• Advisor: Fausto Bruno dos Reis Almeida

Abstract

Cryptococcus neoformans, the causative agent of cryptococcosis, is considered the main fungal pathogen that affects immunocompromised individuals and represents unique model for cell biology studies, due to its unique characteristic of being a eukaryotic pathogen with polysaccharide capsule. Galectin-3 (Gal-3) is an animal lectin that typically binds to ?- galactosides and exerts fine control of various immune functions, including cell adhesion, migration, activation, apoptosis and cytokine secretion, being involved in the immune response innate and adaptive. The present study aimed to evaluate the influence of Gal-3 on C. neoformans infection. We performed survival and quantification of the fungal burden in the lungs and brains of wild type (WT) and knockout for Gal-3 (Gal-3 KO) animals infected with C. neoformans. Gal-3 KO animals were more susceptible to cryptococcosis when compared to WT animals. In addition, when investigating the immune response profile in the brain, lungs, and spleen at 3, 7, and 14 days post-infection from WT and Gal-3 KO, we observed that Gal-3 deficiency affects the Th17 immune response during the experimental infection by C. neoformans.The analysis of the gene profile of innate immunity in the lung, spleen and brain, allowed to infer that, during infection by C. neoformans, Gal-3 is involved in the increase of PRRs responsive to ?-glucan and mannose / chitin (Clec7a and Mrc1), genes related to inflammation (Cxcl1, Cxcl9, Cxcl10, Ccr1, Ccr5, IL-6) and phagocytosis (Sftpd) and decreased expression of CD209a receptor, proinflammatory cytokines IL-12B and IL-1?, and tyrosinekinase involved in signal transduction (Syk). Therefore, our results indicate an important role of Gal-3 in antifungal immunity. (AU)

• FAPESP's process: 16/25167-3 - Influence of galectin-3 on course of infection by Cryptococcus neoformans
• Grantee: Caroline Patini de Rezende
• Support Opportunities: Scholarships in Brazil - Master