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

摘要: Abstract 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, fungal molecules involved in this remain unknown. A. hyphae produce extracellular matrix composed of galactomannan, galactosaminogalactan α-(1,3)-glucan. In study, we investigated consequences UGM1 gene deletion which produces mutant increased production. The ∆ ugm1 exhibited HUVEC-hyperadhesive induced TNF-α secretion tissue factor mRNA overexpression “semi-professional” immune host cell. Using shotgun proteomics approach, show that strain modulate levels proteins important pathways related to mediated by stress pathways. Furthermore, purified fraction was also able coincident HUVEC regulated mutant, overexpresses component, as demonstrated fluorescence microscopy. This work contributes new data regarding mechanisms infection. Significance Invasive aspergillosis is opportunistic infection described neutropenic hematologic patients. One clinical aspect vascular thrombosis, could be related, at least part, activation cells, shown previous reports from our group. It known direct between hyphal cell wall surface necessary pro-inflammatory cytokines, though components angioinvasive fungus trigger are present employs discovery-driven approach reveal role one polysaccharide galactosaminogalactan, interaction consequent activation. first report overall panel specific component .