All ETDs from UAB

Advisory Committee Chair

Phillip D Smith

Advisory Committee Members

Charles O Elson

Laurie E Harrington

Robin G Lorenz

Casey D Morrow

Document Type

Dissertation

Date of Award

2017

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Helicobacter pylori colonizes the stomach of approximately one half of the world’s population. However, the vast majority of infected persons remain asymptomatic. The degree of H. pylori-induced gastric inflammation depends on a complex interaction of several factors. In this dissertation, we focus on age as a determinant of gastritis severity. Children are known to respond to H. pylori infection with a stronger T regulatory cell profile compared with infected adults, yet the reason remains unknown. The influence of the microbiota on, and the communication among, cells of the innate immune system shape the nature of the adaptive immune response to infection. Because H. pylori-induced gastritis is mediated by CD4+ T cells, it is critical to understand the upstream events that determine the precise T cell response to the infection. We show here that the gastric microbiota of H. pylori-infected children differs in abundance of multiple taxa than that of infected adults. Furthermore, we show that pediatric gastric stromal cells down-modulate the dendritic cell response to H. pylori to a greater extent than adult gastric stromal cells. Determining the factor(s) responsible for the protection of children from excessive H. pylori-induced gastritis might facilitate the development of novel therapeutic strategies to treat adults adversely affected by this infection.

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