All ETDs from UAB

Advisory Committee Chair

T Prescott Atkinson

Advisory Committee Members

Li Xiao

Kevin Dybvig

Jessy Deshane

David Chaplin

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Asthma is a chronic respiratory disease associated with small airway obstruction and hy-perreactivity. Greater than 300 million people are estimated to live with asthma world-wide, and in the United States (US), estimated cost-of-care is over $50 billion per year. Allergic sensitization and infections have proven to be important in both asthmatic development, as well as recurrent exacerbations. Diversity and number of bacterial species are increased in asthmatics compared to non-asthmatics, and is also predictive of increased incidence of res-piratory infections. Mycoplasma pneumoniae (Mpn) is an atypical bacterial pathogen of the class Mollicutes, which lacks a cell wall and is an obligate parasite. Mpn has been associat-ed with asthma initiation as well as exacerbation, suggesting that it may play some role in asthmatic pathogenesis. Streptococcus pneumoniae (Spn), is an opportunistic colonizer of the nasopharynx, and the second leading cause of community acquired pneumonia in pedi-atric patients. Evidence has shown that asthmatic individuals have difficulties in mounting robust humoral responses against infection compared to non-asthmatics, therefore, allergic airway sensitization might modulate the host immune response to subsequent bacterial in-fection. Initial studies on optimal means of bacterial disaggregation for enhanced bacterial persistence on Mpn were performed. Mice were sensitized with ovalbumin (OVA) and in-fections were carried out with Mpn and Spn. Immune responses were studied on bron-choalveolar lavage fluid cytokine and cellular infiltrates, and serum antibody levels specific for the respective bacteria. Wild type (Wt) and interleukin-4R knock out (IL-4R KO) animals were examined for the ability to restore anti-bacterial IgG levels to Wt allergically-naïve, infected groups during allergic airway disease model. Finally, Mpn virulence gene expression was analyzed for differences between allergically-naïve and sensitized groups. Virulence gene expression was significantly increased in allergically-sensitized and infected animals compared to naïve controls. Due to the importance of IgG in containing and eradi-cating Mpn in the lung, impairment of the host immune response via allergic airway disease may represent one facet of persistence of Mpn and Spn within this patient population. Fur-ther study of these phenomena will allow for greater understanding of the relationship be-tween allergic airway sensitization and persistent infections with Mpn and Spn.

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