Título:	Murine dendritic cells transcriptional modulation upon Paracoccidioides brasiliensis infection
Autor(es):	Tavares, Aldo Henrique Fonseca Pacheco Derengowski, Lorena da Silveira Ferreira, Karen S. Silva, Simoneide Sousa Macedo, Cláudia Bocca, Anamélia Lorenzetti Passos, Geraldo A Almeida, Sandro R. Ildinete Silva, Pereira
Assunto:	Micoses - Paracoccidioides brasiliensis Células Medula óssea
Data de publicação:	3-Jan-2012
Editora:	Plos One Neglected Tropical Diseases
Referência:	TAVARES, Aldo Henrique Fonseca Pacheco et al. Murine dendritic cells transcriptional modulation upon Paracoccidioides brasiliensis infection. Plos One Neglected Tropical Diseases, v. 6, n. 1, Article e1459, 3 jan. 2012. Disponível em: <http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001459>. Acesso em: 12 jun. 2017. doi: http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001459.
Abstract:	Limited information is available regarding the modulation of genes involved in the innate host response to Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis. Therefore, we sought to characterize, for the first time, the transcriptional profile of murine bone marrow-derived dendritic cells (DCs) at an early stage following their initial interaction with P. brasiliensis. DCs connect innate and adaptive immunity by recognizing invading pathogens and determining the type of effector T-cell that mediates an immune response. Gene expression profiles were analyzed using microarray and validated using real-time RT-PCR and protein secretion studies. A total of 299 genes were differentially expressed, many of which are involved in immunity, signal transduction, transcription and apoptosis. Genes encoding the cytokines IL-12 and TNF-a, along with the chemokines CCL22, CCL27 and CXCL10, were up-regulated, suggesting that P. brasiliensis induces a potent proinflammatory response in DCs. In contrast, pattern recognition receptor (PRR)-encoding genes, particularly those related to Toll-like receptors, were down-regulated or unchanged. This result prompted us to evaluate the expression profiles of dectin-1 and mannose receptor, two other important fungal PRRs that were not included in the microarray target cDNA sequences. Unlike the mannose receptor, the dectin-1 receptor gene was significantly induced, suggesting that this bglucan receptor participates in the recognition of P. brasiliensis. We also used a receptor inhibition assay to evaluate the roles of these receptors in coordinating the expression of several immune-related genes in DCs upon fungal exposure. Altogether, our results provide an initial characterization of early host responses to P. brasiliensis and a basis for better understanding the infectious process of this important neglected pathogen.
Licença:	© 2012 Tavares et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI:	https://dx.doi.org/10.1371/journal.pntd.0001459
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