Helicobacter pylori (H. pylori) infection of the stomach is responsible for significant amount of morbidity and mortality. Although H. pylori have multiple virulence factors, the host response also contributes to pathogenesis and these host factors vary between individuals. In addition to H. py/on-associated diseases, significant morbidity is associated with non-H. pylori associated gastric afflictions. Dyspepsia is the most common gastric ailment among adults and children yet there is no clear association with H. pylori. New genomics evidence on bacterial isolates indicates there are other populations of bacteria in the gastric mucosa. These other bacterial genera or species might help explain why gastric maladies vary between populations and between individuals. They might also serve as an important co-factor in H. py/on-associated diseases. We hypothesize that the gastric mucosa harbors resident populations of non-Helicobacter bacteria that vary among individuals and serve as important cofactors in determining the gastric health of the host. These bacteria, together with the host immune response work cumulatively to influence the incidence and character of gastric malignancies. This hypothesis will be tested by accomplishing the following three specific aims. 1) Compare the immune responses to H. pylori in children and adults undergoing diagnostics for presumptive H. pylori infection. These studies will help us assess the relative importance of the key effector immune responses in influencing the development of H. pylori infection in children and adults. 2. Assess the potential importance of the gastric microbiome in influencing the development and the degree of inflammation associated with H. pylori infection in children and adults. The results from these studies will be correlated with the immune responses in subjects in Aim 1 to determine the association of the gastric microbiome with specific immune responses to H. pylori infection in children and adults. 3. Assess the role of specific immunity and gastric microflora either in isolation or in concert with H. pylori infection, in influencing the development of gastroesophageal reflux disease, dyspepsia, gastric ulcers, duodenal ulcers and gastric cancer. These studies will generate new information about immunologic function and regulation in the stomach which would subsequently allow for comparison to gut immunity. Additionally, new information on the presence and possible contribution of other bacteria on gastric health and disease will provide significant advances for treatment of patients presenting with gastric pathology

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI082655-05
Application #
8485524
Study Section
Special Emphasis Panel (ZAI1-KS-I)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$521,372
Indirect Cost
$159,317
Name
University of Maryland Baltimore
Department
Type
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Salerno-Goncalves, Rosangela; Rezwan, Tasmia; Sztein, Marcelo B (2014) B cells modulate mucosal associated invariant T cell immune responses. Front Immunol 4:511
Fiorentino, Maria; Levine, Myron M; Sztein, Marcelo B et al. (2014) Effect of wild-type Shigella species and attenuated Shigella vaccine candidates on small intestinal barrier function, antigen trafficking, and cytokine release. PLoS One 9:e85211
Waddington, Claire S; Darton, Thomas C; Jones, Claire et al. (2014) An outpatient, ambulant-design, controlled human infection model using escalating doses of Salmonella Typhi challenge delivered in sodium bicarbonate solution. Clin Infect Dis 58:1230-40
Wahid, Rezwanul; Zafar, Shah J; McArthur, Monica A et al. (2014) Live oral Salmonella enterica serovar Typhi vaccines Ty21a and CVD 909 induce opsonophagocytic functional antibodies in humans that cross-react with S. Paratyphi A and S. Paratyphi B. Clin Vaccine Immunol 21:427-34
McArthur, Monica A; Sztein, Marcelo B; Edelman, Robert (2013) Dengue vaccines: recent developments, ongoing challenges and current candidates. Expert Rev Vaccines 12:933-53
Eloe-Fadrosh, Emiley A; McArthur, Monica A; Seekatz, Anna M et al. (2013) Impact of oral typhoid vaccination on the human gut microbiota and correlations with s. Typhi-specific immunological responses. PLoS One 8:e62026
Barry, Eileen M; Pasetti, Marcela F; Sztein, Marcelo B et al. (2013) Progress and pitfalls in Shigella vaccine research. Nat Rev Gastroenterol Hepatol 10:245-55
Eloe-Fadrosh, Emiley A; Rasko, David A (2013) The human microbiome: from symbiosis to pathogenesis. Annu Rev Med 64:145-63
McArthur, Monica A; Sztein, Marcelo B (2013) Unexpected heterogeneity of multifunctional T cells in response to superantigen stimulation in humans. Clin Immunol 146:140-52
Wahid, Rezwanul; Simon, Jakub K; Picking, Wendy L et al. (2013) Shigella antigen-specific B memory cells are associated with decreased disease severity in subjects challenged with wild-type Shigella flexneri 2a. Clin Immunol 148:35-43

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