Título:	Caracterização das bases moleculares da suscetibilidade imunológica à infecção por Candida albicans
Autor(es):	Agustinho, Daniel Paiva
Orientador(es):	Pereira, Ildinete Silva
Coorientador(es):	Tavares, Aldo Henrique Fonseca Pacheco
Assunto:	Candidíase Sistema imunológico
Data de publicação:	12-Nov-2015
Data de defesa:	27-Fev-2015
Referência:	AGUSTINHO, Daniel Paiva. Caracterização das bases moleculares da suscetibilidade imunológica à infecção por Candida albicans. 2015. 98 f., il. Tese (Doutorado em Patologia Molecular)—Universidade de Brasília, Brasília, 2015.
Abstract:	The commensal fungal pathogen Candida albicans can cause lethal systemic infections in immunocompromised patients. One of the main mechanisms of host immune evasion and virulence is the switch to hyphal growth morphologies. Macrophages and monocytes are the inate immune cells that represent the first line of defense against C. albicans infection, and they recognise pathogens via Pattern Recognition Receptors (PRRs). Activation of these receptors induces a signalling pathway that culminates in specific cytokine production, that orchestrates the immune response. Micro RNAs (miRNAs) are considered an essential part of the immune response to a wide variety of pathogens, generally regulating the intensity of this response. miRNAs bind to specific sequences of target mRNAs, thus generally silencing these targets through mRNA degradation or translational repression. This study focused on analyzing the molecular patterns of susceptibility to C. albicans by investigating the differences in gene expression response of two mouse strains, one susceptible and the other resistant to this fungus. Bone marrow-derived macrophages from these strains (DBA/2J and BALB/c, respectively) were co-cultured with C.albicans and their total RNA were extracted and sequenced by RNA-seq. Preliminary analysis of the RNA-seq data validated the quality of obtained sequences and support their use in subsequent steps of comparative characterization of differential transcriptome between resistant and susceptible strains. The next steps will involve the analyses of differentially expressed genes, and their validation by qRT-PCR, as well as interpretation of these data, as a tool for understanding the molecular bases of suceptibility of this medically important pathogen. The next analyses analysis will determine differentially expressed genes which are key to the immune response during the infection by C. albicans. In this work we also analyzed the impact of C. albicans cell morphology upon the modulation of the host miRNA expression. Modulation of the expression of nine different immune response-related miRNAs in primary murine bone marrow-derived macrophages (BMDMs) exposed to either yeast or hyphal forms of C. albicans was investigated. Different growth morphologies were shown to induce distinct miRNA expression patterns in BMDMs. Moreover, our data show that hyphal induction of miR155 in BMDMs is tightly regulated at the transcriptional level during early stages of the host-pathogen interaction. Interestingly, our data suggest that the C-Type lectin receptor Dectin-1 is a major PRR that orchestrates miR155 up regulation in a Syk-dependent manner. These results suggest that PRR-mediated signaling events are key drivers of miRNA-mediated gene regulation during fungal pathogenesis and describe for the first time the signaling pathway likely to be the most important in this process.
Unidade Acadêmica:	Faculdade de Medicina (FM)
Informações adicionais:	Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Patologia Molecular, 2015.
Programa de pós-graduação:	Programa de Pós-Graduação em Patologia Molecular
Licença:	A concessão da licença deste item refere-se ao termo de autorização impresso assinado pelo autor com as seguintes condições: Na qualidade de titular dos direitos de autor da publicação, autorizo a Universidade de Brasília e o IBICT a disponibilizar por meio dos sites www.bce.unb.br, www.ibict.br, http://hercules.vtls.com/cgi-bin/ndltd/chameleon?lng=pt&skin=ndltd sem ressarcimento dos direitos autorais, de acordo com a Lei nº 9610/98, o texto integral da obra disponibilizada, conforme permissões assinaladas, para fins de leitura, impressão e/ou download, a título de divulgação da produção científica brasileira, a partir desta data.
DOI:	http://dx.doi.org/10.26512/2015.02.T.18734
Aparece nas coleções:	Teses, dissertações e produtos pós-doutorado

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