Immunology of Helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies.
Helicobacter pylori infects the stomach of half of the human population worldwide and causes chronic active gastritis, which can lead to peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. The host immune response to the infection is ineffective, because the bacterium persists and the inflammation continues for decades. Bacterial activation of epithelial cells, dendritic cells, monocytes, macrophages, and neutrophils leads to a T helper cell 1 type of adaptive response, but this remains inadequate. The host inflammatory response has a key functional role in disrupting acid homeostasis, which impacts directly on the colonization patterns of H pylori and thus the extent of gastritis. Many potential mechanisms for the failure of the host response have been postulated, and these include apoptosis of epithelial cells and macrophages, inadequate effector functions of macrophages and dendritic cells, VacA inhibition of T-cell function, and suppressive effects of regulatory T cells. Because of the extent of the disease burden, many strategies for prophylactic or therapeutic vaccines have been investigated. The goal of enhancing the host's ability to generate protective immunity has met with some success in animal models, but the efficacy of potential vaccines in humans remains to be demonstrated. Aspects of H pylori immunopathogenesis are reviewed and perspectives on the failure of the host immune response are discussed. Understanding the mechanisms of immune evasion could lead to new opportunities for enhancing eradication and prevention of infection and associated disease.
Wilson
Keith T
KT
Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0252, USA.
Crabtree
Jean E
JE
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology* / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans
D001428:Bacterial Vaccines