Helicobacter pylori Infection and Regulation of the Host Immune Response
Helicobacter pylori Infection and Regulation of the Host Immune Response
US Gastroenterology - Volume 4 - Issue I
Published: January 2009
Published: January 2009
It has been over 20 years since the Gram-negative bacterium Helicobacter pylori was first isolated from the gastric mucosa and its association with malignancies such as gastritis, peptic ulcer disease, and gastric cancer was established.1 Although significant advances have been made in understanding Helicobacter genetics and virulence factors, and in developing efficacious antimicrobial therapies, the means by which H. pylori is able to persist for the life of the host has only recently begun to be elucidated. Although infection induces chronic inflammation and an adaptive immune response, these host defense mechanisms rarely eradicate the bacteria from the stomach. Recent evidence suggests that both the bacterial pathogen and the host itself actively downregulate the immune response. Such activities likely contribute to the persistence of H. pylori at the gastric mucosa.
Suppression of T-cell Activity by Helicobacter pylori
Many factors undoubtedly contribute to the success of H. pylori as a human pathogen. H. pylori possesses several unique virulence factors, but it is also capable of immune evasion as demonstrated by its ability to enter and survive within both host epithelial cells and macrophages. H. pylori has also been shown to limit the activation of T cells. At least two different proteins may contribute to this activity. One is a lowmolecular- weight protein of between 30 and 60kDa that inhibits anti- CD3/CD28-mediated T-cell activation.2 Thus, inhibitory activity could be achieved with whole bacteria and cell-free extracts. The second is the vacuolating cytotoxin of H. pylori (VacA), which has been demonstrated to suppress nuclear factor of activated T cells (NFAT) in transformed T cells, thereby blocking the production of interleukin (IL)-2.3 It was subsequently shown using human primary CD4+ T cells that VacA inhibits cell cycle progression and proliferation independently of IL-2- dependent T-cell survival.4 These studies indicate that H. pylori produces factors that abrogate the H. pylori-specific T-cell response as a means of limiting adaptive immunity, thereby maintaining a microbial niche favorable for survival. Although the bacteria remain separated from the infiltrating T cells by the gastric epithelial cell monolayer, previous studies on patient biopsies have demonstrated that Helicobacter antigens can be found in the lamina propria.
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