Mast Cells Are Critical Mediators of Vaccine-Induced Helicobacter Clearance in the Mouse Model

Abstract

Despite the proven ability of immunization to prevent Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. We explored the cellular events associated with Helicobacter clearance from the stomach following vaccination by flow cytometry analysis and histological and molecular studies. 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 wild-type 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/W v mice showed a negative urease test. Remarkably, vaccinated W/W v 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]). These experiments show that mast cells are, unexpectedly, critical mediators of anti- Helicobacter vaccination.