Replication-Defective Adenovirus Infection ReducesHelicobacter felisColonization in the Mouse in a Gamma Interferon- and Interleukin-12-Dependent Manner
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ABSTRACTHelicobacter infection leads to chronic inflammation of the stomach. Although the infection persists in spite of an immune response, animal studies have shown that adjuvant-based oral vaccines can protect against infection and even eliminate established infection. These vaccines are thought to induce a Th2 immune response, counterbalancing the Th1 response seen with natural infections. As a prelude to using adenovirus vectors carrying cytokine genes to modulate the immune response to establishedHelicobacter felisinfection, we first examined the effect of the replication-defective adenovirus (RDA) vector itself. C57BL/6 mice chronically infected withH. felis(8 to 10 weeks) received intramuscular injections of RDA. The effect of RDA on the severity ofH. feliscolonization and the degree of gastric inflammation was assessed 2 weeks later. RDA caused a significant decrease inH. feliscolonization without significantly altering the associated inflammation. RDA did not alter theH. felis-specific immunoglobulin G1 (IgG1), IgG2a, and IgA responses in the serum but was associated with an increase in gamma interferon (IFN-γ)-producing CD8+spleen cells. To determine if IFN-γ or Th1 cytokines were involved in the response to RDA, we examined RDA treatment ofH. felisinfection in mice lacking either IFN-γ or interleukin-12 (IL-12). RDA failed to alterH. feliscolonization in either of these two mouse strains. Thus, viral infection of mice chronically infected withH. felisled to a significant decrease inH. feliscolonization in an IFN-γ- and IL-12-dependent manner. These results demonstrate that Th1 responses associated with systemic viral infection can influence an establishedH. felisinfection.
