Impact of Mycotoxins Secreted by Aspergillus Molds on the Inflammatory Response of Human Corneal Epithelial Cells

Abstract

Exposure to molds and mycotoxins not only contributes to the onset of respiratory disease, it also affects the ocular surface. Very few published studies concern the evaluation of the effect of mycotoxin exposure on ocular cells. The present study investigates the effects of aflatoxin B1 (AFB1) and gliotoxin, two mycotoxins secreted by Aspergillus molds, on the biological activity of the human corneal epithelial (HCE) cells. After 24, 48, and 72 h of exposure, cellular viability and inflammatory response were assessed. Both endpoint cell viability colorimetric assays and continuous cell impedance measurements, providing noninvasive real-time assessment of the effect on cells, were performed. Cytokine gene expression and interleukin-8 release were quantified. Gliotoxin appeared more cytotoxic than AFB1 but, at the same time, led to a lower increase of the inflammatory response reflecting its immunosuppressive properties. Real-time cell impedance measurement showed a distinct profile of cytotoxicity for both mycotoxins. HCE cells appeared to be a well-suited in vitro model to study ocular surface reactivity following biological contaminant exposure. Low, but persistent inflammation, caused by environmental factors, such as fungal toxins, leads to irritation and sensitization, and could be responsible for allergic manifestations which, in turn, could lead to mucosal hyper-reactivity.

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“…Mercury [31] and environmental toxins [56] are now being linked to immune dysfunction and have been linked to the worldwide increase in autoimmune disease [27], and ADHD [57]. Mold toxins [28] have been associated with chronic fatigue syndrome, upper respiratory illness, and specifically gliotoxins, found in elevated levels in this patient, have been shown to be immunosuppressive [58]. The patient's elevated C4a level and TGFB-1 levels are biomarkers seen with Chronic Inflammatory Response Syndrome (CIRS) associated with mold exposure and brain injury [59].…”

Precision Medicine: The Role of the MSIDS Model in Defining, Diagnosing, and Treating Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome and Other Chronic Illness: Part 2

“…Coinfections, like Mycoplasma [34] and Bartonella [239,240], as well as environmental toxins have also been associated with immunological dysfunction. Mycoplasmas can interact with B cells [33], affecting antibody production, and mercury [50], along with other environmental toxins [51] (including gliotoxins, which have been shown to be immunosuppressive), have been linked to immune dysfunction and a worldwide increase in autoimmune disease [37,241].…”

Impact of Air Pollution and Weather on Dry Eye

“…Similar to the human studies [ 36 , 37 , 39 , 40 ], organic bioaerosols have also been reported to negatively impact ocular surface health. In an in-vitro study, human corneal epithelial (HCE) cells were exposed to various concentrations of mycotoxins (AFB 1 and gliotoxin) vs. a solvent control, and in vitro assays were done to asses cellular viability and inflammatory responses [ 45 ]. Exposure to AFB 1 (16 µg/mL) increased expression of several inflammatory markers (380-fold increase in IL-8, 160-fold increase in C-X-C motif chemokine ligand 1, 21-fold increase in TNF-α) compared to the control.…”