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Allergens and their associated small molecule ligands-their dual role in sensitization.

ABSTRACT: Many allergens feature hydrophobic cavities that allow the binding of primarily hydrophobic small-molecule ligands. Ligand-binding specificities can be strict or promiscuous. Serum albumins from mammals and birds can assume multiple conformations that facilitate the binding of a broad spectrum of compounds. Pollen and plant food allergens of the family 10 of pathogenesis-related proteins bind a variety of small molecules such as glycosylated flavonoid derivatives, flavonoids, cytokinins, and steroids in vitro. However, their natural ligand binding was reported to be highly specific. Insect and mammalian lipocalins transport odorants, pheromones, catecholamines, and fatty acids with a similar level of specificity, while the food allergen β-lactoglobulin from cow's milk is notably more promiscuous. Non-specific lipid transfer proteins from pollen and plant foods bind a wide variety of lipids, from phospholipids to fatty acids, as well as sterols and prostaglandin B2, aided by the high plasticity and flexibility displayed by their lipid-binding cavities. Ligands increase the stability of allergens to thermal and/or proteolytic degradation. They can also act as immunomodulatory agents that favor a Th2 polarization. In summary, ligand-binding allergens expose the immune system to a variety of biologically active compounds whose impact on the sensitization process has not been well studied thus far.

SUBMITTER: Chruszcz M

PROVIDER: S-EPMC8286345 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The environment plays an instrumental role in the developmental origins of health and disease. Protective features of the environment in the development of asthma and atopy have been insufficiently studied. We used data from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study to examine relationships between living near natural green spaces in early infancy in Edmonton, AB, Canada and the development of atopic sensitization at 1 year and 3 years of age in a cohort of 699 infants, and whether these associations were mediated by infant gut microbiota (measured using 16s V4 amplicon sequencing) at 4 months. The Urban Planning Land Vegetation Index (uPLVI) map of the City of Edmonton was used to assess infants' exposure to natural spaces based on their home postal codes, and atopic sensitization was assessed using skin prink testing (SPTs) for common food and inhalant allergens. Our findings suggest there is a protective effect of natural green space proximity on the development of multiple inhalant atopic sensitizations at 3 years (odds ratio = 0.28 [95% CI 0.09, 0.90]). This relationship was mediated by changes to Actinobacteria diversity in infant fecal samples taken at 4 months. We also found a positive association between nature proximity and sensitization to at least one food or inhaled allergen; this association was not mediated by gut microbiota. Together, these findings underscore the importance of promoting natural urban greenspace preservation to improve child health by reducing atopic disease susceptibility. IMPORTANCE Our findings highlight the importance of preserving natural green space in urban settings to prevent sensitization to environmental allergens and promote early-life gut microbiota pathways to this health benefit. These findings support a mediating role of gut microbiome compositions in health and disease susceptibility. This study used unique, accurate, and comprehensive methodology to classify natural space exposure via a high-resolution topographical map of foliage subtypes within the City of Edmonton limits. These methods are improvements from other methods previously used to classify natural space exposure, such as the normalized density vegetation index from satellite imagery, which is not able to distinguish anthropogenic from green space. The use of these methods and the associations found between natural green space exposure and atopic sensitization outcomes support their use in future studies. Our findings also provide many avenues for future research including longer term follow up of this cohort and investigation of a causal role of reduced Actinobacteria diversity on atopic sensitization development.

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Allergens and their associated small molecule ligands-their dual role in sensitization.

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