Eradication of Helicobacter spp. by using medicated diet in mice deficient in functional natural killer cells and complement factor D

Abstract

A commercial 4-drug diet has shown promise in eradicating Helicobacter spp. from rodents; however, its effectiveness in immunocompromised mice is unknown. This study evaluated the efficacy of this treatment in eradicating Helicobacter spp. from mice deficient in functional natural killer cells (Cd1(-/-)) or complement factor D (Df(-/-)). Cd1(-/-) mice naturally infected with H. hepaticus with or without H. rodentium were fed either control or medicated diet for 8 wk followed by 4 wk on control diet. Fecal samples were PCR-evaluated for Helicobacter spp. before mice began treatment and then every 2 wk thereafter for 12 wk. The same experimental design was repeated for eighteen 9- to 21-wk-old Df(-/-) mice naturally infected with H. bilis with or without H. rodentium. All Df(-/-) mice and 8- to 21-wk-old Cd1(-/-) mice ceased shedding Helicobacter spp. after 2 wk of treatment and remained negative throughout the study. In contrast, the Cd1(-/-) mice that were 24 wk or older shed Helicobacter spp. for the first 8 wk but tested negative at 10 and 12 wk. All treated animals had enlarged ceca and gained less weight than control untreated mice, and 6 of 7 treated Cd1(-/-) male mice developed mild portal fibrosis. These findings show that within 2 wk of treatment, the 4-drug diet eradicated H. hepaticus and H. rodentium from young Cd1(-/-) mice and H. bilis and H. rodentium from Df(-/-) mice, but eradication of established infections in Cd1(-/-) mice required 8 wk of treatment.

Figure 1.

Control Cd1^−/− male mice gained significantly (P < 0.0001) more weight than did treated Cd1^−/− male mice. Data are given as mean ± SEM.

Figure 2.

Treated mice (right) had significantly (P < 0.0001) larger ceca than did control mice.

Figure 3.

Representative sample of mild portal fibrosis in treated Cd1^−/− mice. Hematoxylin and eosin stain; scale bar, 100 μm.