Mast cells are critical mediators of vaccine-induced Helicobacter clearance in the mouse model

Background & Aims: Despite the proven ability of immunization to prevent Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. Methods: We explored the cellular events associated with Helicobacter clearance from the stomach following vaccination by flow cytometry analysis and histological and molecular studies. Results: Kinetic studies showed that the infection is undetectable in vaccinated mice at day 5 postbacterial challenge. Flow cytometry analysis showed that the percentages of mast cells (CD3(-)CD117(+)) increased in the lymphoid cells isolated from the stomach at day 4 postchallenge in urease + cholera toxin (CT)-vaccinated mice in comparison with mice administered with CT alone (9.4% +/- 4.4% and 3.1% +/- 1%, respectively, for vaccinated and CT administered, n = 5; P < .01). Quantitative PCR analysis showed an increased messenger RNA (mRNA) expression of the mast cell proteases :1 and 2 at day 5 postchallenge in the stomach of vaccinated mice. In contrast to wildtype mice, mast cell-deficient mice (W/W-v mice) were not protected from H felis colonization after vaccination. Indeed only 1 out of 12 vaccinated W/Wv mice showed a negative urease test. Remarkably, vaccinated W/Wv mice reconstituted with cultured bone marrow-derived mast cells recovered the ability to clear the infection after vaccination (8 out of 10 mast cell-reconstituted mice showed negative urease tests [P < .006 as compared with wild-type mice]). Conclusions: These experiments show that mast cells are, unexpectedly, critical mediators of anti-Helicobacter vaccination.