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

Helicobacter infection leads to chronic inflammation of the stomach. Althou gh the infection persists in spite of an immune response, animal studies ha ve shown that adjuvant-based oral vaccines can protect against infection an d even eliminate established infection. These vaccines are thought to induc e a Th2 immune response, counterbalancing the Th1 response seen with natura l infections. As a prelude to using adenovirus vectors carrying cytokine ge nes to modulate the immune response to established Helicobacter felis infec tion, we first examined the effect of the replication-defective adenovirus (RDA) vector itself. C57BL/6 mice chronically infected with H. felis (8 to 10 weeks) received intramuscular injections of RDA, The effect of RDA on th e severity of H, felis colonization and the degree of gastric inflammation was assessed 2 weeks later. RDA caused a significant decrease in H. felis c olonization without significantly altering the associated inflammation. RDA did not alter the H. felis-specific immunoglobulin G1 (IgG1), IgG2a, and I gA responses in the serum but was associated with an increase in gamma inte rferon (IFN-gamma)-producing CD8(+) spleen cells. To determine if IFN-gamma or Th1 cytokines were involved in the response to RDA, we examined RDA tre atment of H, felis infection in mice lacking either IFN-gamma or interleuki n-12 (IL-12), RDA failed to alter H, felis colonization in either of these two mouse strains. Thus, viral infection of mice chronically infected with H, felis led to a significant decrease in H, felis colonization in an IFN-y gamma and IL-12-dependent manner. These results demonstrate that Th1 respo nses associated with systemic viral infection can influence an established H, felis infection.