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

ABSTRACT

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-1ß (IL-1ß). 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 macrophage model. Abbreviations AF A. fumigatus, Aspergillus fumigatus; AV A. versicolor, Aspergillus versicolor; AM Airway Macrophage; CBA Cytometric Bead Array; CD Cluster of Differentiation; DTT dithiothreitol; ELISA Enzyme Linked Immunosorbent Assay; FBS fetal bovine serum; GM-CSF Granulocyte macrophage colony-stimulating factor; IL-1ß Interleukin-1beta; MDM Monocyte-Derived Macrophages; NF-κB Nuclear Factor kappa light chain enhancer of activated B cells; NLR NOD-like Receptor; PAMP Pathogen Associated Molecular Pattern; PMA Phorbol 12-myristate 13-acetate; PRR Pattern Recognition Receptor; THP-1 Human leukemia monocyte cell line; TLR Toll-like Receptor; TNF-α Tumor Necrosis Factor- alpha.