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Environmental mold and mycotoxin exposures elicit specific cytokine and chemokine responses
Jamie H Rosenblum Lichtenstein1, Yi-Hsiang Hsu2, Igor M Gavin3
1Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America; Institute for Liberal Arts, Emerson College, Boston, MA, United States of America.
Background:
Molds can cause respiratory symptoms and asthma. We sought to use isolated peripheral blood mononuclear cells (PBMCs) to understand changes in cytokine and chemokine levels in response to mold and mycotoxin exposures and to link these levels with respiratory symptoms in humans. We did this by utilizing an ex vivo assay approach to differentiate mold-exposed patients and unexposed controls. While circulating plasma chemokine and cytokine levels from these two groups might be similar, we hypothesized that by challenging their isolated white blood cells with mold or mold extracts, we would see a differential chemokine and cytokine release.
Methods And Findings:
Peripheral blood mononuclear cells (PBMCs) were isolated from blood from 33 patients with a history of mold exposures and from 17 controls. Cultured PBMCs were incubated with the most prominent Stachybotrys chartarum mycotoxin, satratoxin G, or with aqueous mold extract, ionomycin, or media, each with or without PMA. Additional PBMCs were exposed to spores of Aspergillus niger, Cladosporium herbarum and Penicillium chrysogenum. After 18 hours, cytokines and chemokines released into the culture medium were measured by multiplex assay. Clinical histories, physical examinations and pulmonary function tests were also conducted. After ex vivo PBMC exposures to molds or mycotoxins, the chemokine and cytokine profiles from patients with a history of mold exposure were significantly different from those of unexposed controls. In contrast, biomarker profiles from cells exposed to media alone showed no difference between the patients and controls.
Conclusions:
These findings demonstrate that chronic mold exposures induced changes in inflammatory and immune system responses to specific mold and mycotoxin challenges. These responses can differentiate mold-exposed patients from unexposed controls. This strategy may be a powerful approach to document immune system responsiveness to molds and other inflammation-inducing environmental agents.
Insights
Mold and mycotoxin exposure alters immune cell responses. Isolated white blood cells from mold-exposed individuals showed distinct cytokine and chemokine profiles compared to controls, potentially aiding in diagnosis.
Area of Science:
- Immunology
- Environmental Health
- Respiratory Medicine
Background:
- Molds and mycotoxins are known triggers for respiratory symptoms and asthma.
- Assessing immune responses to mold exposure is crucial for understanding health impacts.
- Current methods may not fully capture the immune system's reaction to environmental mold challenges.
Purpose of the Study:
- To investigate changes in cytokine and chemokine levels in peripheral blood mononuclear cells (PBMCs) following mold and mycotoxin exposure.
- To differentiate between mold-exposed patients and unexposed controls using an ex vivo cellular assay.
- To correlate immune response profiles with respiratory symptoms in humans.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were isolated from 33 mold-exposed patients and 17 controls.
- PBMCs were cultured and exposed ex vivo to specific mycotoxins (satratoxin G), mold extracts, and common mold spores (Aspergillus niger, Cladosporium herbarum, Penicillium chrysogenum).
- Cytokine and chemokine release into the culture medium was measured using multiplex assays after 18 hours.
Main Results:
- Ex vivo exposure of PBMCs to molds or mycotoxins resulted in significantly different cytokine and chemokine profiles in mold-exposed patients compared to controls.
- No significant differences were observed between groups when PBMCs were exposed to media alone.
- These distinct cellular responses suggest a measurable impact of chronic mold exposure on immune function.
Conclusions:
- Chronic mold exposure induces lasting changes in immune and inflammatory responses.
- The observed differential immune cell responsiveness can distinguish mold-exposed individuals from unexposed controls.
- This ex vivo assay approach offers a promising method for documenting immune system reactivity to environmental agents like molds.
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