Pro-inflammatory responses induced by A. fumigatus and A. versicolor in various human macrophage models

Exposure to mold-contaminated indoor air has been associated with various respiratory diseases, and there is a need for experimental data to confirm these associations. The pro-inflammatory properties of well-characterized aerosolized spores and hyphal fragments from Aspergillus fumigatus and Aspergillus versicolor were examined and compared using various human macrophage cell models including phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages (THP-1 Ma), primary peripheral blood monocyte-derived macrophages (MDM), and primary airway macrophages (AM) from induced sputum. X-ray treated samples of the two mold species induced different responses with A. fumigatus displaying the most potent induction of pro-inflammatory responses. While hyphal fragments from A. fumigatus were more potent than spores, similar responses were produced by the two growth stages of A. versicolor. THP-1 Ma was the most sensitive model releasing a broad range of cytokines/chemokines. MDM exhibited a similar cytokine/chemokine profile as THP-1 Ma, except for a low-quantity release of interleukin-1β (IL-1β). In contrast, AM appeared to be nonresponsive and yielded a different pattern of pro-inflammatory markers. Toll-like receptor (TLR)4, but also to a certain degree TLR2, was involved in several responses induced by spores and aerosolized hyphal fragments of A. fumigatus in MDM. Taken together, MDM seems to be the most promising experimental...