Modifications to the composition of the hyphal outer layer of Aspergillus fumigatus modulates HUVEC proteins related to inflammatory and stress responses

Autor: Gabriela W. P. Neves, Leila M. Lopes-Bezerra, Paula H. Kubitschek-Barreira, Gustavo H. Goldman, Marcel Lyra Cunha, Thierry Fontaine, Jean-Paul Latgé, Nathalia Curty, Gustavo H.M.F. Souza, Anne Beauvais
Přispěvatelé: Universidade do Estado do Rio de Janeiro [Rio de Janeiro] (UERJ), Aspergillus, Institut Pasteur [Paris], MS Applications Research and Development Laboratory, Waters Corporation, Waters Technologies Brazil, Faculdade de Ciências Farmacêuticas de Ribeirão Preto [São Paulo], Universidade de São Paulo (USP), This work was supported bythe Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ),grants E-26/100.329/2014 and E-26/102819/2012. LMLB is a research fellow of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Faperj, and GWPN is a PhD Nota 10 fellow of FAPERJ., Institut Pasteur [Paris] (IP), Universidade de São Paulo = University of São Paulo (USP)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Journal of Proteomics
Journal of Proteomics, Elsevier, 2017, 151, pp.83-96. ⟨10.1016/j.jprot.2016.06.015⟩
Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
Journal of Proteomics, 2017, 151, pp.83-96. ⟨10.1016/j.jprot.2016.06.015⟩
ISSN: 1874-3919
1876-7737
DOI: 10.1016/j.jprot.2016.06.015⟩
Popis: Aspergillus fumigatus , the main etiologic agent causing invasive aspergillosis, can induce an inflammatory response and a prothrombotic phenotype upon contact with human umbilical vein endothelial cells (HUVECs). However, the fungal molecules involved in this endothelial response remain unknown. A. fumigatus hyphae produce an extracellular matrix composed of galactomannan, galactosaminogalactan and α-(1,3)-glucan. In this study, we investigated the consequences of UGM1 gene deletion in A. fumigatus , which produces a mutant with increased galactosaminogalactan production. The ∆ ugm1 mutant exhibited an HUVEC-hyperadhesive phenotype and induced increased endothelial TNF-α secretion and tissue factor mRNA overexpression in this “semi-professional” immune host cell. Using a shotgun proteomics approach, we show that the A. fumigatus ∆ ugm1 strain can modulate the levels of proteins in important endothelial pathways related to the inflammatory response mediated by TNF-α and to stress response pathways. Furthermore, a purified galactosaminogalactan fraction was also able to induce TNF-α secretion and the coincident HUVEC pathways regulated by the ∆ ugm1 mutant, which overexpresses this component, as demonstrated by fluorescence microscopy. This work contributes new data regarding endothelial mechanisms in response to A. fumigatus infection. Significance Invasive aspergillosis is the main opportunistic fungal infection described in neutropenic hematologic patients. One important clinical aspect of this invasive fungal infection is vascular thrombosis, which could be related, at least in part, to the activation of endothelial cells, as shown in previous reports from our group. It is known that direct contact between the A. fumigatus hyphal cell wall and the HUVEC cell surface is necessary to induce an endothelial prothrombotic phenotype and secretion of pro-inflammatory cytokines, though the cell surface components of this angioinvasive fungus that trigger this endothelial response are unknown. The present work employs a discovery-driven proteomics approach to reveal the role of one important cell wall polysaccharide of A. fumigatus , galactosaminogalactan, in the HUVEC interaction and the consequent mechanisms of endothelial activation. This is the first report of the overall panel of proteins related to the HUVEC response to a specific and purified cell wall component of the angioinvasive fungus A. fumigatus .
Databáze: OpenAIRE
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