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Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection (DCs Gene Expression in P. brasiliensis Infection)

Tavares, Aldo H ; Derengowski, Lorena S ; Ferreira, Karen S ; Silva, Simoneide S ; Macedo, Cláudia ; Bocca, Anamélia L ; Passos, Geraldo A ; Almeida, Sandro R ; Silva-Pereira, Ildinete Kamhawi, Shaden (Editor)

PLoS Neglected Tropical Diseases, 2012, Vol.6(1), p.e1459 [Periódico revisado por pares]

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  • Título:
    Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection (DCs Gene Expression in P. brasiliensis Infection)
  • Autor: Tavares, Aldo H ; Derengowski, Lorena S ; Ferreira, Karen S ; Silva, Simoneide S ; Macedo, Cláudia ; Bocca, Anamélia L ; Passos, Geraldo A ; Almeida, Sandro R ; Silva-Pereira, Ildinete
  • Kamhawi, Shaden (Editor)
  • Assuntos: Research Article ; Biology ; Genetics And Genomics ; Immunology ; Microbiology
  • É parte de: PLoS Neglected Tropical Diseases, 2012, Vol.6(1), p.e1459
  • Descrição: 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-α, 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 β-glucan 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. ; Paracoccidioidomycosis is a systemic disease that has an important mortality and morbidity impact in Latin America, mainly affecting rural workers of Argentina, Colombia, Venezuela and Brazil. Upon host infection, one of the most important aspects contributing to disease outcome is the initial encounter of the fungus with dendritic cells. This phagocytic cell is specialized in decoding microbial information and triggering specific immune responses. Thus, using a molecular biology technique to examine the response of thousand of genes, we aimed to identify the ways in which murine dendritic cells interact with during an early time point following infection. This approach allowed us to recognize diverse modulated genes, in particular those associated with a proinflamatory response and fungal recognition. Our work provides an initial molecular characterization of early infection process and should promote further investigations into the innate host response to this important fungal pathogen.
  • Idioma: Inglês

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