Mohammad S. Alam

Vaccine-induced immunity against Helicobacter pylori in the absence of IL-17A

Background:  Helicobacter pylori (H. pylori) is a gram negative bacterium that can cause diseases such as peptic ulcers and gastric cancer. IL‐17A, a proinflammatory cytokine that can induce the production of CXC chemokines for neutrophil recruitment, has recently been shown to be elevated in both H. pylori‐infected patients and mice. Furthermore, studies in mouse models of vaccination have reported levels significantly increased over infected, unimmunized mice and blocking of IL‐17A during the challenge phase in immunized mice reduces protective immunity. Because many aspects of immunity had redundant or compensatory mechanisms, we investigated whether mice could be protectively immunized when IL‐17A function is absent during the entire immune response using IL‐17A and IL‐17A receptor knockout (KO) mice immunized against H. pylori.

Host Immunity in the Development of Gastric Preneoplasia

Correa proposed a sequence of events that were associated with the development of gastric cancer that included gastritis as one of the earliest phases of a multistep process (Correa and Houghton 2007) (Figure 17.1). With the identification of Helicobacter pylori, it quickly became apparent that infection caused the gastritis that subsequently led to gastric preneoplasia and the development of gastric cancer in a subset of infected subjects. Several important issues have emanated from these observations including the role of the host response in the persistence of H. pylori infection and, given the chronic nature of the infection and inflammation, the role of immune and inflammatory factors in the pathogenesis of gastric cancer itself. This chapter reviews the initial immunologic responses that lead to gastritis and explains the persistence of infection. The consequence of chronic inflammation on epithelial cell damage that may lead to gastric neoplasia is discussed in the context of animal models and translational studies that have shed light on our understanding of the pathogenesis of diseases associated with H. pylori infection.