Pro-inflammatory cytokine gene expression in the stomach correlates with vaccine-induced protection against Helicobacter pylori infection in mice: an important role for interleukin-17 during the effector phase. : Immune correlates to H. pylori protection

• CD4(+) T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection in mice. Less is known about relative contributions of individual cell subpopulations, such as TH1 and TH17 cells, and their associated cytokines. The aim of the present study was to find immune correlates to vaccine-induced protection and further study their role in protection against H. pylori infection. Immunized and unimmunized mice were challenged with H. pylori and immune responses were compared. Vaccine-induced protection was assessed by measuring H. pylori colonization in the stomach. Gastric gene expression of TH1- and/or TH17-associated cytokines was analyzed by quantitative PCR and contributions of individual cytokines to protection were evaluated by antibody-mediated in vivo neutralization. By analyzing immunized and unimmunized mice a significant inverse correlation could be demonstrated between levels of interleukin (IL)-12p40, tumor necrosis factor α (TNF), interferon γ (IFNγ) and IL-17 gene expression and number of H. pylori in the stomach of individual animals after challenge. In a kinetic study, up-regulation of TNF, IFNγ and IL-17 coincided with vaccine-induced protection 7 days after H. pylori challenge and was sustained for at least 21 days. In vivo neutralization of these cytokines during the effector phase of the immune response revealed a significant role for IL-17, but not for IFNγ or TNF, in vaccine-induced protection. In conclusion, although both TH1- and TH17-associated gene expression in the stomach correlate with vaccine-induced protection against H. pylori infection, our study indicates that mainly TH17 effector mechanisms are of critical importance to protection.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Helicobacter pylori

vaccine

mouse

IFNγ

IL-17

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)