Pro-Inflammatory Responses in Human Bronchial Epithelial Cells Induced by Spores and Hyphal Fragments of Common Damp Indoor Molds

Abstract

Damp indoor environments contaminated with different mold species may contribute to the development and exacerbation of respiratory illnesses. Human bronchial epithelial BEAS-2B cells were exposed to X-ray treated spores and hyphal fragments from pure cultures of Aspergillus fumigatus, Penicillum chrysogenum, Aspergillus versicolor and Stachybotrys chartarum. Hyphal fragments of A. fumigatus and P. chrysogenum induced expression and release of the pro-inflammatory cytokine interleukin (IL)-6 and the chemokine IL-8, while none of the other hyphal preparations had effects. Hyphal fragments from A. fumigatus and P. chrysogenum also increased the expression of IL-1α, IL-1β and tumor necrosis factor (TNF)-α, but these cytokines were not released. X-ray treated spores had little or no inflammatory potential. Attenuating Toll-like receptor (TLR)-2 by blocking antibodies strongly reduced the A. fumigatus and P. chrysogenum hyphae-induced IL-6 and IL-8 release, whereas TLR4 antagonist treatment was without effects. Untreated A. fumigatus spores formed hyphae and triggered expression of pro-inflammatory genes with similarities to the effects of hyphal fragments. In conclusion, while X-ray treated spores induced no pro-inflammatory responses, hyphal fragments of A. fumigatus and P. chrysogenum enhanced a TLR2-dependent expression and release of IL-6 and IL-8.

New Approach Methods to Evaluate Health Risks of Air Pollutants: Critical Design Considerations for In Vitro Exposure Testing

“…These cells can differentiate into squamous cells in response to certain substances, which make them amenable for screening chemicals that may induce or affect cell differentiation processes potentially relevant to carcinogenesis [55]. Studies using BEAS-2B cells have identified alterations in cell differentiation signaling in response to PM 2.5 [56], indoor molds [57], and diesel exhaust particles [58].…”

Bronchial Epithelial Cells on the Front Line to Fight Lung Infection-Causing Aspergillus fumigatus

“…Using a silencing method, it has been demonstrated that TLR2, in a heterodimer form with TLR1 or TLR6, is required for the expression of Dectin-1 by HBE cells in response to A. fumigatus infection (29). Moreover, blocking TLR2 with antibodies results in the inhibition of the release of IL-6 and IL-8 by BEAS-2B cells infected with A. fumigatus hyphal fragments (59). Certain polymorphisms in TLR4, receptor for the bacterial lipopolysaccharide, are clearly associated with increased susceptibility to invasive aspergillosis (60).…”

“…TLR4 expressed by mouse macrophages, recognizes A. fumigatus conidia and hyphae and induces the release of pro-inflammatory molecules. However, after blocking TLR4 with a specific monoclonal antibody, Øya et al failed to detect any significant change in the levels of IL-6 and IL-8 released by BEAS-2B cells infected with X-ray-treated hyphal fragments of A. fumigatus (59). Hypomethylated DNA, the natural ligand of TLR9, has been extracted in A. fumigatus hyphae (61).…”

Characterization and pro‐inflammatory potential of indoor mold particles

“…Actually, the inflammatory potential of A fumigatus hyphal fragments was higher than the two less pathogenic species tested. In strong contrast to A fumigatus , spores of P chrysogenum germinated poorly in vitro . A mouse study found that resting A fumigatus spores formed germ tubes in the lung tissue rapidly after inhalation, whereas no signs of germination of A versicolor spores were seen .…”