Aspergillus fumigatus, an airborne pathogen, causes many diseases, including aspergilloma, invasive aspergillosis, and allergic bronchopulmonary aspergillosis. Phospholipase D (PLD) is an important virulence factor for A. fumigatus infection, but the manner by which PLD contributes to the virulence of this pathogen is not clear. Our results show that expression of A. fumigatus PLD in human cells was able to increase the production of reactive oxygen species (ROS), which play an important role in several signaling pathways as well as in lung infection. Meanwhile, A. fumigatus PLD was found to interact with human endogenous histone deacetylase 6 (HDAC6), a known regulator of ROS production and inflammatory responses; PLD significantly increased the expression level of HDAC6 protein without altering its mRNA level. These results suggest that A. fumigatus PLD may enhance the production of ROS via the accumulation of HDAC6, which may be involved in host immunomodulation during A. fumigatus infection. (C) 2018 Elsevier Inc. All rights reserved.