Environmental Mold and Mycotoxin Exposures Elicit Specific Cytokine and Chemokine Responses

Lichtenstein, Jamie H. Rosenblum; Hsu, Yi Hsiang; Gavin, Igor M.; Donaghey, Thomas C.; Molina, Ramon M.; Thompson, Khristy J.; Lin, Chih Chung; Gillis, Bruce S.; Brain, Joseph D.

doi:10.1371/journal.pone.0126926

Cited by 28 publications

(30 citation statements)

References 88 publications

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“…These cytokines may also be altered in humans exposed to S. chartarum or other molds (9). IL-5 is associated with increased eosinophil response (59).…”

Section: Altered Cytokinesmentioning

confidence: 99%

“…We recently demonstrated several patterns of responses to mold in humans (9). Isolated human peripheral blood mononuclear cells were exposed to mycotoxins ex vivo.…”

Section: Mouse-human Data Correlationsmentioning

confidence: 99%

“…We compared responses to single and multiple doses of S. chartarum to the cytokine and chemokine profiles that have been previously reported in humans with a history of mold exposures (9).…”

mentioning

confidence: 99%

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Repeated Mouse Lung Exposures toStachybotrys chartarumShift Immune Response from Type 1 to Type 2

Lichtenstein¹,

Molina²,

Donaghey³

et al. 2016

Am J Respir Cell Mol Biol

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After a single or multiple intratracheal instillations of Stachybotrys chartarum (S. chartarum or black mold) spores in BALB/c mice, we characterized cytokine production, metabolites, and inflammatory patterns by analyzing mouse bronchoalveolar lavage (BAL), lung tissue, and plasma. We found marked differences in BAL cell counts, especially large increases in lymphocytes and eosinophils in multipledosed mice. Formation of eosinophil-rich granulomas and airway goblet cell metaplasia were prevalent in the lungs of multiple-dosed mice but not in single-or saline-dosed groups. We detected changes in the cytokine expression profiles in both the BAL and plasma. Multiple pulmonary exposures to S. chartarum induced significant metabolic changes in the lungs but not in the plasma. These changes suggest a shift from type 1 inflammation after an acute exposure to type 2 inflammation after multiple exposures to S. chartarum. Eotaxin, vascular endothelial growth factor (VEGF), MIP-1a, MIP-1b, TNF-a, and the IL-8 analogs macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemoattractant (KC), had more dramatic changes in multiplethan in single-dosed mice, and parallel the cytokines that characterize humans with histories of mold exposures versus unexposed control subjects. This repeated exposure model allows us to more realistically characterize responses to mold, such as cytokine, metabolic, and cellular changes.

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“…These cytokines may also be altered in humans exposed to S. chartarum or other molds (9). IL-5 is associated with increased eosinophil response (59).…”

Section: Altered Cytokinesmentioning

confidence: 99%

“…We recently demonstrated several patterns of responses to mold in humans (9). Isolated human peripheral blood mononuclear cells were exposed to mycotoxins ex vivo.…”

Section: Mouse-human Data Correlationsmentioning

confidence: 99%

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Repeated Mouse Lung Exposures toStachybotrys chartarumShift Immune Response from Type 1 to Type 2

Lichtenstein¹,

Molina²,

Donaghey³

et al. 2016

Am J Respir Cell Mol Biol

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“…Positive tests have to be in accordance with a plausible relationship between the patient’s complaints and his exposure history in order to avoid false-positive associations. These results are not only due to possible irrelevant cross-reactivity or methodological issues but also because the presence of IgE is not a necessary indicator of mold exposure (10). A major problem is on the other side, the lack of measurable scientific evidence, when patients and doctors see a plausible correlation of mold exposure and attributed health problems without having specific biomarkers of exposure, which support the claimed interrelation.…”

Section: Introductionmentioning

confidence: 99%

An Evolutionary-Based Framework for Analyzing Mold and Dampness-Associated Symptoms in DMHS

Daschner

2017

Front. Immunol.

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Among potential environmental harmful factors, fungi deserve special consideration. Their intrinsic ability to actively germinate or infect host tissues might determine a prominent trigger in host defense mechanisms. With the appearance of fungi in evolutionary history, other organisms had to evolve strategies to recognize and cope with them. Existing controversies around dampness and mold hypersensitivity syndrome (DMHS) can be due to the great variability of clinical symptoms but also of possible eliciting factors associated with mold and dampness. An hypothesis is presented, where an evolutionary analysis of the different response patterns seen in DMHS is able to explain the existing variability of disease patterns. Classical interpretation of immune responses and symptoms are addressed within the field of pathophysiology. The presented evolutionary analysis seeks for the ultimate causes of the vast array of symptoms in DMHS. Symptoms can be interpreted as induced by direct (toxic) actions of spores, mycotoxins, or other fungal metabolites, or on the other side by the host-initiated response, which aims to counterbalance and fight off potentially deleterious effects or fungal infection. Further, individual susceptibility of immune reactions can confer an exaggerated response, and magnified symptoms are then explained in terms of immunopathology. IgE-mediated allergy fits well in this scenario, where individuals with an atopic predisposition suffer from an exaggerated response to mold exposure, but studies addressing why such responses have evolved and if they could be advantageous are scarce. Human history is plenty of plagues and diseases connected with mold exposure, which could explain vulnerability to mold allergy. Likewise, multiorgan symptoms in DMHS are analyzed for its possible adaptive role not only in the defense of an active infection, but also as evolved mechanisms for avoidance of potentially harmful environments in an evolutionary past or present setting.

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“…Antecubital blood was drawn into BD Cell Preparation Tubes (Becton Dickinson, Franklin Lakes, NJ) containing sodium heparin, and PBMCs were isolated by density-gradient centrifugation according to the manufacturer’s instructions, and dispensed into 12-well culture plates in the presence of several different mitogen configurations. First, to measure Th-1 vs. Th-2 cytokine production following non-specific stimulation, we incubated 0.5x10 6 PBMCs with 25 ng/mL of phorbol 12-myristate 13-acetate (PMA; Sigma-Aldrich, St. Louis, MO) + 1 ug/mL of ionomycin (INO; Sigma-Aldrich, St. Louis, MO) for 24 hours at 37°C in 5% CO 2 , similar to previous studies (39, 40, 63). An unstimulated well with the same number of PBMCs but no mitogen was cultured under the same conditions.…”

Section: Methodsmentioning

confidence: 89%

Dimensions of Socioeconomic Status and Childhood Asthma Outcomes: Evidence for Distinct Behavioral and Biological Associations

et al. 2016

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Objective This study investigated two key dimensions of socioeconomic status (SES) – prestige and resources – and their associations with immune, behavioral, and clinical outcomes in childhood asthma. Methods Children ages 9–17 with a physician diagnosis of asthma (N=150) and one of their parents participated in this study. Children and parents completed interviews and questionnaires about SES (prestige=parent education; resources=family assets), environmental exposures, and clinical asthma measures. Spirometry was conducted to assess children’s pulmonary function, and blood was collected to measure cytokine production in response to non-specific stimulation, allergen-specific stimulation, and microbial stimulation. Results Higher scores on both dimensions of childhood SES were associated with better clinical outcomes in children (β’s from |.18–.27|, p values <.05). Higher prestige, but not resources, was associated with better home environment control behaviors and less exposure to smoke (β’s from |.21 to .22|, p values<.05). Higher resources, but not prestige, was associated with more favorable immune regulation, as manifest in smaller peripheral blood mononuclear cell (PBMC) Th-1 and Th-2 cytokine responses (β’s from −.18 to −.19, p values <.05), and smaller pro-inflammatory cytokine responses (β =−.19, p<.05) following ex vivo stimulation. Higher resources also were associated with more sensitivity to glucocorticoid inhibition of Th-1 and Th-2 cytokine production (β’s from −.18 to −.22, p values <.05). Conclusion These results suggest that prestige and resources in childhood family environments have different implications for behavioral and immunological processes relevant to childhood asthma. They also suggest that childhood SES relates to multiple aspects of immunologic regulation of relevance to the pathophysiology of asthma.

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Environmental Mold and Mycotoxin Exposures Elicit Specific Cytokine and Chemokine Responses

Cited by 28 publications

References 88 publications

Repeated Mouse Lung Exposures toStachybotrys chartarumShift Immune Response from Type 1 to Type 2

Repeated Mouse Lung Exposures toStachybotrys chartarumShift Immune Response from Type 1 to Type 2

An Evolutionary-Based Framework for Analyzing Mold and Dampness-Associated Symptoms in DMHS

Dimensions of Socioeconomic Status and Childhood Asthma Outcomes: Evidence for Distinct Behavioral and Biological Associations

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