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Gastroenterology. 2009 Jan;136(1):247-56. doi: 10.1053/j.gastro.2008.09.017. Epub 2008 Sep 20.

Vaccination of mice against H pylori induces a strong Th-17 response and immunity that is neutrophil dependent.

Author information

1
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Abstract

BACKGROUND & AIMS:

Vaccine efficacy against gastric Helicobacter pylori infection has been shown in mice, but little is known about the mechanisms of bacterial clearance. Our aim was to investigate a possible T-cell/neutrophil pathway of vaccine-induced protection.

METHODS:

Nonimmune and immunized mice were compared for their response to H pylori challenge. T-cell responses were assessed by recall assays. Interleukin (IL)-17-induced chemokine production was evaluated by cytokine enzyme-linked immunosorbent assay. In a kinetic study, biopsy specimens were collected at multiple time points postchallenge and assessed for bacterial load and inflammation. Relative levels of T cells, IL-17, interferon gamma, MIP-2, KC, and LIX were determined by quantitative polymerase chain reaction. The role of neutrophils was evaluated by antibody-mediated depletion of neutrophils following challenge.

RESULTS:

Immunization induced strong interferon gamma- and IL-17-producing T-cell responses, and IL-17 was capable of inducing significant amounts of KC and MIP-2 from dendritic cells, macrophages, fibroblasts, and gastric epithelial cells. Challenge of immunized mice induced significantly greater gastritis than that of infected mice, preceding significantly lower bacterial loads by day 7. In immune mice, T-cell recruitment to the gastric mucosa correlated with a continuous rise in IL-17 and interferon gamma levels, followed by KC, MIP-2, and LIX production and the recruitment of significant numbers of neutrophils by day 5. Antibody-mediated depletion of neutrophils abrogated vaccine efficacy.

CONCLUSIONS:

Vaccination of mice against H pylori results in a significant Th-17 cell recall response associated with increases in chemokines that attract neutrophils to the stomach, which are important for eradication of H pylori.

PMID:
18948106
PMCID:
PMC4960660
DOI:
10.1053/j.gastro.2008.09.017
[Indexed for MEDLINE]
Free PMC Article

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