Replication-defective adenovirus infection reduces Helicobacter felis colonization in the mouse in a gamma interferon- and interleukin-12-dependent manner.

摘要: Helicobacter infection leads to chronic inflammation of the stomach. Although persists in spite an immune response, animal studies have shown that adjuvant-based oral vaccines can protect against and even eliminate established infection. These are thought induce a Th2 counterbalancing Th1 response seen with natural infections. As prelude using adenovirus vectors carrying cytokine genes modulate felis infection, we first examined effect replication-defective (RDA) vector itself. C57BL/6 mice chronically infected H. (8 10 weeks) received intramuscular injections RDA. The RDA on severity colonization degree gastric was assessed 2 weeks later. caused significant decrease without significantly altering associated inflammation. did not alter felis-specific immunoglobulin G1 (IgG1), IgG2a, IgA responses serum but increase gamma interferon (IFN-g)-producing CD8 1 spleen cells. To determine if IFN-g or cytokines were involved RDA, treatment lacking either interleukin-12 (IL-12). failed these two mouse strains. Thus, viral led IFN-g- IL-12-dependent manner. results demonstrate systemic influence pylori causes gastritis, has causal role development peptic ulcers, is considered risk factor for cancer mucosa-associated lymphoid tissue lymphomas (34). Once established, it develops. Eradication cure ulcer prevention its recurrence (47). Studies suggest given mucosal adjuvant such as cholera toxin prevent lead elimination (6, 8, 12). Cholera induces shift helper T-cell from Th1- Th2-type response. been proposed responsible induction protection, also mixed (17, 43) (4). Therefore, possibility remains use adjuvants like heatlabile enterotoxin Escherichia coli humans potentially toxicity, preliminary data clinical effectiveness disappointing (36). alternative means modulating need be explored. We others injection inflammatory number infectious agents allergens (21, 33, 41, 44). availability recombinant containing immunomodulatory molecules provides alternate approach modulation present study designed effects itself model.