Microbes in the mucosa: impacts of the mucosal immune system and oral vaccination with Lactobacillus acidophilus on the gut microbiome
Date
2021
Authors
Fox, Bridget E., author
Dean, Gregg, advisor
Abdo, Zaid, advisor
Tobet, Stuart, committee member
Ryan, Elizabeth, committee member
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Abstract
The mucosal immune system is constantly balancing between the clearance of pathogens, tolerance of self-antigen and food, and maintenance of homeostasis within the microbiota. Vaccination via mucosal routes is advantageous because it provides protection at local mucosal sites and systemically. However, induction of efficacious responses are often difficult due to the inherent barriers of the mucosal tissues. We have developed a probiotic-based mucosal vaccination platform that utilizes recombinant Lactobacillus acidophilus (rLA) to overcome these obstacles presented in oral vaccination. Here, we sought to determine whether repeated administration of rLA alters the intestinal microbiome as a result of L. acidophilus probiotic activity (direct competition and selective exclusion) or from the host's mucosal immune response against the rLA vaccine. To address the latter, IgA-seq was employed to characterize shifts in IgA-bound bacterial populations. Additionally, we determined whether using rice bran as a prebiotic would influence the immunogenicity of the vaccine and/or IgA bound bacterial populations. Our results show that the prebiotic influenced the kinetics of rLA antibody induction, and that the rLA platform does not cause lasting disturbances to the microbiome. Nucleotide-binding oligomerization domain containing 2 (NOD2) has presented itself as an essential regulator of immune responses within the gastrointestinal tract. This innate immune receptor is expressed by several cell types, including both hematopoietic and nonhematopoietic cells within the gastrointestinal tract. Mice harboring knockouts of NOD2 only in CD11c+ cells were used to better characterize NOD2 signaling during mucosal vaccination with rLA. We show that NOD2 signaling in CD11c+ cells is critical for mounting a humoral immune response against rLA. Additionally, disruption of NOD2 signaling in CD11c+ cells results in an altered bacterial microbiome profile in both vaccinated and unvaccinated mice.
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Subject
mucosal immunology
probiotic
oral vaccine
microbiome