Angiogenesis at the mold-host interface: a potential key to understanding and treating invasive aspergillosis

Invasive aspergillosis (IA) in neutropenic patients is characterized by angioinvasion, intravascular thrombosis and tissue infarction, features that lead to sequestration of infected tissue and impaired fungal clearance. Recent research has shown that host angiogenesis, the homeostatic compensatory response to tissue hypoxia, is downregulated by Aspergillus fumigatus secondary metabolites. A. fumigatus metabolites inhibit multiple key angiogenic mediators, notably basic FGF, VEGF and their respective receptors. Moreover, repletion of basic FGF and VEGF enhances angiogenesis at the site of infection, induces trafficking of polymorphonuclear leukocytes into fungal-infected tissue and enhances antifungal drug activity. This review summarizes the emerging roles of vasculopathy and angiogenesis in the pathogenesis of IA, emphasizing the importance of the underlying mode of immunosuppression. Modulation of angiogenesis is a potential target for novel therapeutic strategies against IA.