Helicobacter pylori vaccines and mechanisms of effective immunity: is mucus the key?
In this theoretical article, the hypothesis is proposed that immunization against gastric helicobacter infection is mediated by CD4+ T-cell induced changes in mucus production. Vaccine development for the gastric pathogen Helicobacter pylori has encountered several problems. Resolving these problems is impeded by our lack of understanding of the mechanisms by which the immune response influences bacterial colonization. Protective immunity requires CD4+ T cells, but the majority of helicobacters are located in the mucus of the gastric lumen, away from the epithelial surface. Evidence suggests that this mechanism functions independently of antibodies, so how this is achieved is unknown. Clues to this mechanism may be provided by immune clearance of nematode infection. Similar to H. pylori, expulsion of the intestinal nematode, Nippostrongylus brasiliensis, in rodents is mediated by CD4+ T-cell changes in the numbers of goblet cells and the type of mucins secreted into the gut. Immune-mediated changes in secretion of gastric mucins could similarly be responsible for the reductions in helicobacter colonization seen in immunized animals. Helicobacter pylori are highly motile bacteria that have evolved to inhabit their specialized niche. Alterations in their mucus environment could influence their motility, such that the bacteria cannot remain efficiently within the mucus and are flushed away.
Sutton
P
P
School of Microbiology and Immunology, University of New South Wales, Sydney, New South Wales, Australia. P.sutton@unsw.edu.au
D000818:Animals; D001422:Bacterial Adhesion; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D009077:Mucins / Q000378:metabolism*; D009559:Nippostrongylus / Q000276:immunology; D051381:Rats; D017206:Strongylida Infections / Q000276:immunology / Q000469:parasitology; D014611:Vaccination
D001428:Bacterial Vaccines; D009077:Mucins