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Abstract

Burkholderia pseudomallei, a gram negative, soil-borne, bacterium, is the causative agent of melioidosis. Melioidosis causes a serve pneumonic disease that results in mortality in 54% of cases each year. The most prominent risk factor involved in 39% of melioidosis cases is a recent binge alcohol intoxication episode. In our most recent publication, we found that biologically relevant concentrations of a binge alcohol episode led to a dysfunction in the innate immune system, specifically, alveolar macrophages ability to clear a near neighbor, bacterium, B. thailandensis. There has not been any research conducted to investigate the effects of binge alcohol on the adaptive immune system, specifically, alcohol’s effects on the humoral immune response during an active infection. Using B. thailandensis as a phylogenetically similar bacterium to B. pseudomallei and B. vietnamiensis an opportunistic pathogen within the Burkholderiaceae family, we were able to better understand the risk factor of binge alcohol intoxication and its effects on the humoral immune response during infection. We hypothesized that binge alcohol intoxication would lead to a dysfunction in the humoral immune response resulting in the inability for mice to clear the infection. Consistent with our previous studies, binge alcohol intoxication showed to delay the humoral immune response, specifically the ability of immunoglobulins to class switch from IgM to IgG immunoglobulins. With mice exposed to alcohol, IgM and IgG were significantly decreased at each time point, with IgM remaining the predominant antibody throughout 28 days. Finally, binge alcohol intoxication lead to an alteration in the specificity of IgM and IgG when targeting specific bacterial antigens, that being, the whole cell lysate, capsular polysaccharide, and the lipopolysaccharide-A. The suppression of the humoral immune response played a role in the mortality in mice and a prolonged infection.

Details

Title
Binge Alcohol Intoxication Impacts on the Humoral Immune Response Against Burkholderia spp. Infections
Author
Moreno, Ryan M.
Year
2018
Publisher
ProQuest Dissertations & Theses
ISBN
978-0-438-01571-5
Source type
Dissertation or Thesis
Language of publication
English
ProQuest document ID
2054025532
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.