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Whole Allergen

m7 Botrytis cinerea

m7 Botrytis cinerea Scientific Information

Type:

Whole Allergen

Display Name:

Botrytis cinerea

Route of Exposure:

Inhaled

Family:

Sclerotiniaceae

Species:

cinerea

Latin Name:

Botrytis cinerea

Other Names:

Gray mold (1) Wine growers lung (2)

Summary

Botrytis cinerea is a ubiquitous, necrotrophic, phytopathic fungus. It poses a significant economic burden worldwide through spoilage of various crops pre-and post-harvest. B. cinerea has a low prevalence in both outdoor and indoor environments, despite there being a high prevalence of sensitization. B. cinerea causes allergic rhinitis in children and adults, asthma in children and hypersensitivity pneumonitis in the horticultural and viticultural settings. There is currently no recognized B. cinerea allergen.

Allergen

Nature

B. cinerea is a necrotrophic, phytopathogenic fungus (3). It is unusual for the botrytis genera in its ability to colonize over 200 species of mainly dicotyledenous plants in temperate and subtropical regions (4). Furthermore, B. cinerea produces sclerotia that survive in the environment for many years (3). It is a Leotiomycetes powdery mildew fungus (3), and it forms gray colonies, from which it takes the colloquial name ”gray mold” (5). Morphologically, the B. cinerea conidiophore resembles a cluster of grapes (botryose) (6).

B. cinerea is the cause of substantial pre- and post-harvest crop spoilage and economic cost (7). It affects nursery plants, vegetables, and orchard crops (8) and is the cause of the familiar grey mold seen on strawberries (6). B. cinerea is also resistant to pesticide treatment, which is attributed to the fungus’ unusually diverse phenotype (9). Conversely, B. cinerea is of commercial value in viniculture, where its fermentation action on grapes is used to produce a sweetened, concentrated wine (8).

Apart from its’ allergen potential, B. cinerea is not considered pathogenic to humans (8). B. cinerea–specific allergens are reported causative agents in Severe Asthma with Fungal Sensitization (SAFS) and hypersensitivity pneumonitis associated with occupational exposure, “Wine-growers’ lung” (2). B. cinerea causes a relatively high prevalence of sensitization, despite having a low airborne prevalence (10). 

Taxonomy

Taxonomic tree of B. cinerea (6)

Domain

Eukaryote

Kingdom

Fungi

Phylum

 Ascomycota

Subphylum

Pezizomycotina (4)

Class

Leotiomycetes

Order

Heliotiales

Family

Sclerotiniaceae

Genus

Botrytis

Taxonomic tree of B. cinerea (6)

Epidemiology

Worldwide distribution 

B. cinerea is found globally, with geographically dependent spore seasons. It has a low prevalence in ambient air both indoors and outdoors, with a calculated median of around 1.1% across different environments. However, this was reported to be higher in the Netherlands, at between 2.7–17% (7).

Sensitization to B. cinerea antigen among patients with clinical hypersensitivity is estimated to range from 1.3% to 52%, with a calculated median of 18.1%, as determined by skin prick or radioallergosorbent test (7). Similarly, the reported prevalence of sensitivity to B. cinerea in a cohort of patients with severe asthma was 18%, although this was always with co-sensitization with at least one other fungal allergen (11).

Furthermore, it has been demonstrated that B. cinerea is the most prevalent allergen in mold-sensitized patients in the USA and the second most prevalent allergen amongst patients in Denmark and Sweden (8).

The prevalence of sensitization to B. cinerea in the occupational setting has also been evaluated. A study of greenhouse workers in the Netherlands found 4% of chrysanthemum workers and 13.8% bell pepper workers (7).

Environmental Characteristics

Living environment

The indoor prevalence of B. cinerea in damp-free households is estimated between 0–4.8%, and prevalence in damp homes ranges between 0.9–5.5%, with a calculated median of 2%. This is higher than the calculated median for damp-free indoor and environments (1.1%), providing evidence of increased Botrytis levels in damp homes (7).

B. cinerea is a hydrophilic fungus and needs a minimum water activity of 0.9 (aw, max = 1, an objective measure of the unbound water content of the substrate which supports mold growth (12)) It has also been demonstrated that airflow and relative humidity (RH) are important factors that mediate the release of fungal particles into the airspace. Low RH (18–40%) resulted in more fungal (1-3)-β-D-glucan and chitinase being aerosolized than high RH (60–80%) conditions. This indicates that respirable particles are released at a lower RH. The average RH in British homes is estimated to be 43% in living rooms and 49% in bedrooms. In the experimental setting, the largest number of B. cinerea particles was aerosolized at low RH.

In the occupational setting, several studies have demonstrated that any activity that results in air movement, as is typical with most horticultural tasks, results in a significant release of B. cinerea conidia into the airspace (7).

Route of Exposure

Main 

Airborne exposure has been reported globally (8).

Secondary

Exposure by the oral route has been proposed with ingestion of fruit and vegetables with surface B. cinerea, which can persist after washing (7). Additionally, a role for B. cinerea allergens in the pathogenesis of wine hypersensitivity has been proposed. However, there is no documented evidence of this (13).

Clinical Relevance

B. cinerea has been associated with allergic rhinitis and asthma (14). SAFS is a hypersensitivity syndrome characterized by allergic sensitization to fungi and the resulting modulating effect on asthma, with chronic fungal bronchitis resulting in mucosal damage and airway remodeling. There is overlap with allergic bronchopulmonary aspergillosis (ABPA), however, a significant difference is that ABPA is rarely diagnosed in children with asthma. Central to the diagnosis of SAFS is the demonstration of sensitization (skin prick test wheal ≥3mm or Specific IgE ≥0.4) to at least one of seven fungal species, one of which is B. cinerea (Bush, 2020). Hypersensitivity pneumonitis has been reported in a case study of two vinery workers (Wine-grower’s lung) in Austria (7). 

Molecular Aspects

Allergenic molecules

There are no B. cinerea-specific allergens recognized by the WHO IUIS Allergen Nomenclature Sub-committee.

It has been proposed that, in common with other fungi, the cell wall carbohydrates of B. cinerea may play a role in the pathogenesis of allergic airway disease (7). Fungal β-glucans promote allergic sensitization to co-administered antigens in the lung (15). A study in a murine model has shown that co-exposure of a high molecular weight allergen with Avicularia versicolor spores results in a more severe asthma phenotype. Furthermore, the immune response was altered by the presence of fungus, with enhanced Th2 cell response and an additional Th17 response (16). Chitin could also play a role, with high chitin expressing fungal isolates eliciting increased airway eosinophilia (16).

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Christian  Fischer 

 

Last reviewed: February 2022

References
  1. Green BJ. Emerging Insights into the Occupational Mycobiome. Current Allergy and Asthma Reports. 2018;18(11):62.
  2. Dutkiewicz J, Cisak E, Sroka J, Wójcik-Fatla A, Zając V. Biological agents as occupational hazards – selected issues. Ann Agric Environ Med. 2011;18(2):286-93.
  3. Amselem J, Cuomo CA, van Kan JA, Viaud M, Benito EP, Couloux A, et al. Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea. PLoS Genet. 2011;7(8):e1002230.
  4. Williamson B, Tudzynski B, Tudzynski P, Van Kan JAL. Botrytis cinerea: the cause of grey mould disease. Molecular Plant Pathology. 2007;8(5):561-80.
  5. Li D-W, Lamondia J. Airborne fungi associated with ornamental plant propagation in greenhouses. Aerobiologia. 2009;26:15-28.
  6. Levetin E, Horner WE, Scott JA, Barnes C, Baxi S, Chew GL, et al. Taxonomy of Allergenic Fungi. The Journal of Allergy and Clinical Immunology: In Practice. 2016;4(3):375-85.e1.
  7. Jurgensen CW, Madsen A. Exposure to the airborne mould Botrytis and its health effects. Ann Agric Environ Med. 2009;16(2):183-96.
  8. Hashimoto S, Tanaka E, Ueyama M, Terada S, Inao T, Kaji Y, et al. A case report of pulmonary Botrytis sp. infection in an apparently healthy individual. BMC Infectious Diseases. 2019;19(1):684.
  9. Chardonnet CO, Sams CE, Trigiano RN, Conway WS. Variability of Three Isolates of Botrytis cinerea Affects the Inhibitory Effects of Calcium on this Fungus. Phytopathology. 2000;90(7):769-74.
  10. Madsen AM. Effects of Airflow and Changing Humidity on the Aerosolization of Respirable Fungal Fragments and Conidia of Botrytis cinerea. Appl Environ Microbiol. 2012;78(11):3999-4007.
  11. O'Driscoll BR, Powell G, Chew F, Niven RM, Miles JF, Vyas A, et al. Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma. Clinical & Experimental Allergy. 2009;39(11):1677-83.
  12. Saldanha R, Manno M, Saleh M, Ewaze JO, Scott JA. The influence of sampling duration on recovery of culturable fungi using the Andersen N6 and RCS bioaerosol samplers. Indoor Air. 2008;18(6):464-72.
  13. Wüthrich B. Allergic and intolerance reactions to wine. Allergol Select. 2018;2(1):80-8.
  14. Esch RE, Codina R. Fungal raw materials used to produce allergen extracts. Ann Allergy Asthma Immunol. 2017;118(4):399-405.
  15. Roy RM, Klein BS. Fungal glycan interactions with epithelial cells in allergic airway disease. Curr Opin Microbiol. 2013;16(4):404-8.
  16. Zhang Z, Reponen T, Hershey GK. Fungal Exposure and Asthma: IgE and Non-IgE-Mediated Mechanisms. Curr Allergy Asthma Rep. 2016;16(12):86.