VacA and HP-NAP, Ying and Yang of Helicobacter pylori-associated gastric inflammation.
Helicobacter pylori is a Gram-negative bacterium which infects almost half of the population worldwide and represents the major cause of gastroduodenal pathologies, such as duodenal and gastric ulcer, gastric cancer, B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) and autoimmune gastritis. H. pylori colonization is followed by infiltration of the gastric mucosa by polymorphonuclear cells, macrophages and lymphocytes. Two of the major H. pylori virulence factors are the vacuolating cytotoxin (VacA) and the H. pylori neutrophil-activating protein (HP-NAP). VacA has been proposed as a modulator of immune cell function because of its capacity to interfere with antigen presentation and to inhibit T-cell activation. HP-NAP was designated as neutrophil-activating protein because it stimulates high production of oxygen radicals from neutrophils. We have recently demonstrated that HP-NAP is able to recruit leukocytes in vivo and to stimulate either neutrophils or monocytes to release IL-12, a key cytokine for the differentiation of naive Th cells into the Th1 phenotype. Altogether these evidences indicate that both VacA and HP-NAP play a major role in generating and maintaining the gastric inflammatory response associated with the H. pylori infection.
D'Elios
Mario Milco
MM
Department of Internal Medicine, University of Florence, Florence, Italy.
Montecucco
Cesare
C
de Bernard
Marina
M
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002448:Cell Adhesion; D004847:Epithelial Cells / Q000187:drug effects; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D013276:Stomach Ulcer / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; C092412:neutrophil-activating protein A, Helicobacter pylori