Project description:Foxp3+ regulatory T cells (Treg) play a central role for tolerance against self and innocuous environmental antigens. However, the role of antigen-specificity for Treg-mediated tolerance is only incompletely understood. Here we show by direct ex vivo characterization of human CD4+ T cells, that the response against innocuous airborne antigens, such as plant pollen or fungal spores, is dominated by memory-like antigen-specific Treg. Surprisingly, breakdown of tolerance in atopic donors was not accompanied by a quantitatively or qualitatively altered Treg response, but instead correlated with a striking dichotomy of Treg versus Th2 target specificity. Allergenic proteins, are selectively targeted by Th2 cells, but not Treg. Thus human Treg specific for airborne antigens maintain tolerance at mucosal sites and the failure to generate specific Treg against a subgroup of antigens provides a window of opportunity for allergy development. PBMCs from sex and age matched birch pollen allergic patients and healthy controls, were stimulated (7h) with airborne fungal (A. fumigatus) or birch pollen antigen (birch) and sorted into antigen specific conventional and regulatory T cells according to their expression of CD154+ and CD137+ on CD4+ T cells, respectively. Number of samples per group in parentheses: Healthy controls stimulated with A. fumigatus (n=5), allergic patients stimulated with A. fumigatus (n=6), healthy controls stimulated with birch (n=6), allergic patients stimulated with birch (n=4).
Project description:Shellfish processing workers are highly susceptible to respiratory illnesses such as allergies and asthma. However, the airborne biological exposures in this industry are not well characterized. This study aimed at identifying and quantifying airborne biological exposures in the shrimp processing industry and assessing their impact on human health. Our findings show that shrimp processing workers are exposed to several allergenic proteins and irritants. High levels of the major shrimp allergen tropomyosin were detected, with the cooking and peeling departments identified as high-exposure areas. Moreover, workers had a high prevalence of respiratory symptoms and elevated levels of selected biomarkers of asthma and allergy which correlated with the measured total airborne protein levels in their work environment. Our study provides important novel evidence showing the occupational burden of airborne biological exposures in the shrimp industry and identifying critical work task. Altogether, the results underscore the need for improved targeted protective measures.
Project description:We report changes in H3K27ac following LPS stimulation in Detroit 562 cells. We were able to identified LPS-increased H3K27ac regions which correlated with RELA binding as well as gene up-regulation. This data set is relevant for airborne bacterial sensing as Detroit 562 cells are nasopharyngeal epithelial cells and LPS is a gram negative bacterial endotoxin.
Project description:The study aimed at evaluation and comparison of airway epithelium mRNA profile in response to airborne particulate matter presented by macrophages using in vitro triple cell co-culture model.
Project description:Increase in the occurrence and severity of human H5N1 spillover infections resulting from dissemination of highly pathogenic avian influenza (HPAI) virus into bird and mammal populations raises concerns about HPAI adapting to become human transmissible. Studies identified hemagglutinin acid stability and receptor preference as essential molecular traits that shape host tropism. Mutations that increase hemagglutinin acid-stability and affinity for a-2,6-linked sialic acids have been shown to confer H5N1 airborne transmissibility in a ferret model. Here, we use hydrogen/deuterium-exchange mass spectrometry to dissect how airborne adaptation mutations impact dynamics during activation. Our results reveal that such mutations suppress dynamics in pH-responsive regions including the fusion peptide and receptor binding and fusion subunit interface, which would prevent premature inactivation during airborne transmission. These results for HPAI hemagglutinin identify regions that are hotspots for adaptive changes and reveal general influenza subtype-specific patterns.