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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2020.tde-19092019-125830
Document
Author
Full name
Caroline Patini de Rezende
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2019
Supervisor
Committee
Almeida, Fausto Bruno dos Reis (President)
Lucas, Rosymar Coutinho de
Luzente, Fernanda Patrícia Gullo
Rossi, Nilce Maria Martinez
Title in Portuguese
Influência de galectina-3 no curso da infecção por Cryptococcus neoformans
Keywords in Portuguese
Cryptococcus neoformans
Expressão gênica
Galectina-3
Abstract in Portuguese
Cryptococcus neoformans, agente causador da criptococose, é considerado o principal patógeno fúngico que acomete indivíduos imunodeprimidos e representa modelo único para estudos de biologia celular, por sua singular característica de ser um patógeno eucarioto com cápsula polissacarídica. Galectina-3 (Gal-3) é uma lectina animal que se liga tipicamente em ?-galactosídeos e exerce o controle fino de várias funções imunológicas, incluindo adesão celular, migração, ativação, apoptose e secreção de citocinas, estando envolvida na resposta imune inata e adaptativa. O presente estudo teve como objetivo avaliar a influência de Gal-3 na infecção por C. neoforrmans. Foi avaliada a sobrevida e quantificada a carga fúngica no pulmão e cérebro de animais selvagens (WT) e knockout para Gal-3 (Gal-3 KO) infectados com C. neoformans. Os animais Gal-3 KO foram mais suscetíveis a criptococose quando comparado aos animais WT. Também foi investigado o perfil de resposta imune no pulmão, baço e cérebro em 3, 7 e l4 dias pós-infecção nos animais WT e Gal-3 KO, e verificado que a deficiência de Gal-3 afeta o perfil de resposta imune Thl7 durante a infecção experimental por C. neoformans. A análise do perfil gênico da imunidade inata no pulmão, baço e cérebro permitiu inferir, que durante infecção por C. neoformans, Gal-3 está envolvida no aumento da expressão de PRRs responsivos a ?-glucana e manose/quitina (Clec7a e Mrcl), de genes relacionados a inflamação (Cxcl1, Cxcl9, Cxcl10, Ccrl, CcrS, IL-6) e fagocitose (Sftpd) e diminuição da expressão do receptor CD209a, das citocinas pro-inflamatórias IL-12B e IL-l? e da tirosina- quinase envolvida na transdução de sinal (Syk). Nossos resultados indicam envolvimento de Gal-3 na imunidade antifúngica.
Title in English
Influence of galectina-3 on the course of infection by Cryptococcus neoformans
Keywords in English
Cryptococcus neoformans
Galectin-3
Gene expression
Abstract in English
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.
 
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Publishing Date
2020-01-15
 
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