Date of Award
Spring 5-15-2023
Additional Affiliations
University College
Degree Name
Master of Arts (AM/MA)
Degree Type
Thesis
Abstract
Allergic rhinitis is one of the most common chronic illnesses in America, affecting more than 60 million people each year. Allergies develop when sensitization to an environmental allergen result in the production of antigen-specific IgE. Subsequent exposure to the allergen, detected by IgE, then binds to the surface of mast cells triggering the release of inflammatory mediators particularly histamine, which contribute to characteristic allergic symptoms of nasal itching, sneezing, and wheezing. Although fundamental mechanisms underlying allergy development have been previously characterized, recent research has implicated commensal bacteria residing in the respiratory tract in contributing to the development of allergic inflammation, yet the mechanisms by which these microbes affect the host is unknown. Through comparative genomic analysis of bacterial isolates from nasopharyngeal lavage samples, we found Haemophilus species are enriched in the airways of asthmatics compared to healthy controls. These Haemophilus strains encode for a putative histidine decarboxylase (HDC), which is known to convert histidine into histamine. In vitro testing reveals hdc expressing Haemophilus can produce histamine from histidine, as well as commonly encountered aeroallergens, such as pollen, mold, and dog/cat dander. I developed a mouse model to study the physiological response these hdc+ strains of Haemophilus exhibit to the host. These data show that histamine production by hdc+ airway bacteria can induce signs of rhinitis, including sneeze, demonstrating that airway commensals have the potential to induce non-IgE mediated rhinitis.
Language
English (en)
Chair and Committee
Andrew Kau, Internal Medicine
Committee Members
Ian Duncan, Drew Schwartz
Signed Thesis Approval Form
Thesis_for_Submission_postedits (2).docx (5786 kB)
Recommended Citation
Lint, Michael, "Histamine production by airway resident Haemophilus species induces rhinitis" (2023). Arts & Sciences Electronic Theses and Dissertations. 2957.
https://openscholarship.wustl.edu/art_sci_etds/2957
Comments
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