title: Discovering the infectome of human endothelial cells challenged with Aspergillus fumigatus applying a mass spectrometry label-free approach.
abstract: Blood vessel invasion is a key feature of invasive aspergillosis. This angioinvasion process contributes to tissue thrombosis, which can impair the access of leukocytes and antifungal drugs to the site of infection. It has been demonstrated that human umbilical vein endothelial cells (HUVECs) are activated and assume a prothrombotic phenotype following contact with Aspergillus fumigatus hyphae or germlings, a process that is independent of fungus viability. However, the molecular mechanisms by which this pathogen can activate endothelial cells, together with the endothelial pathways that are involved in this process, remain unknown. Using a label-free approach by High Definition Mass Spectrometry (HDMS(E)), differentially expressed proteins were identified during HUVEC-A. fumigatus interaction. Among these, 89 proteins were determined to be up- or down-regulated, and another 409 proteins were exclusive to one experimental condition: the HUVEC control or HUVEC:AF interaction. The in silico predictions provided a general view of which biological processes and/or pathways were regulated during HUVEC:AF interaction, and they mainly included cell signaling, immune response and hemostasis pathways. This work describes the first global proteomic analysis of HUVECs following interaction with A. fumigatus germlings, the fungus morphotype that represents the first step of invasion and dissemination within the host.
  
  
  CONCLUSIONS
  A. fumigatus causes the main opportunistic invasive fungal infection related to neutropenic hematologic patients. One of the key steps during the establishment of invasive aspergillosis is angioinvasion but the mechanism associated with the interaction of A. fumigatus with the vascular endothelium remains unknown. The identification of up- and down-regulated proteins expressed by human endothelial cells in response to the fungus infection can contribute to reveal the mechanism of endothelial response and, to understand the physiopathology of this high mortality disease. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.
authors.affiliation: Laboratório de Micologia Celular e Proteômica, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.
authors.forename: N
authors.initials: N
authors.lastname: Curty
authors.affiliation: Laboratório de Micologia Celular e Proteômica, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.
authors.forename: P H
authors.initials: PH
authors.lastname: Kubitschek-Barreira
authors.affiliation: Laboratório de Micologia Celular e Proteômica, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.
authors.forename: G W
authors.initials: GW
authors.lastname: Neves
authors.affiliation: Laboratório de Micologia Celular e Proteômica, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Gomes
authors.affiliation: Laboratório de Células-Tronco, Divisão de laboratórios do CEMO, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Pizzatti
authors.affiliation: Laboratório de Células-Tronco, Divisão de laboratórios do CEMO, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Abdelhay
authors.affiliation: MS Applications Research and Development Laboratory, Waters Corporation, São Paulo, Brazil.
authors.forename: G H M F
authors.initials: GH
authors.lastname: Souza
authors.affiliation: Laboratório de Micologia Celular e Proteômica, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil. Electronic address: leila@uerj.br.
authors.forename: L M
authors.initials: LM
authors.lastname: Lopes-Bezerra
mesh_terms: D001228:Aspergillosis / Q000378:metabolism* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D020543:Proteome / Q000378:metabolism*
chemical_list: D020543:Proteome
keywords: A. fumigatus; Endothelial cell; HUVEC; Infectome; Invasive aspergillosis; NanoLC-HDMS(E)