Upregulation of innate and adaptive immune mechanisms facilitating prevention of gastric infection in guinea pigs by administration of chitosan microparticles loaded with BCG.

[BACKGROUND] () rods frequently colonize and damage the gastric mucosa in humans, causing inflammation, gastric or duodenal ulcers and even gastric cancer. negatively modulates the activity of immune cells, including macrophages and lymphocytes facilitating the persistence of infection. Increasing resistance of isolates to commonly used antibiotics diminishes the success of therapy. These prompt searches for new therapeutic formulations to improve the effectiveness of immune mechanisms against . Based on the previous studies indicating the immunomodulatory properties of (Bacillus Calmette-Guérin) BCG vaccine bacilli, we developed chitosan microparticles-(CHI MPs) modified with N-acetylglucosamine-(G) or with Pluronic F-127-(P) to facilitate the delivery and persistence of live BCG in the stomach and in the gut of susceptible to infection.

[METHODS] Animals (5/per group) were inoculated only with CHI MPs, G or P variant or both, or with such CHI MPs and then with the reference CCUG17874 positive for cytotoxin-associated gene A-() (3 times in two-day intervals). Control animals received only (positive control) or broth (negative control). Two assessment points have been selected: 7 and 28 days after the last inoculation, mimicking early and chronic infection, respectively.

[RESULTS] The gastric tissue of guinea pigs (4/5) receiving G/P CHI MPs loaded with BCG before inoculation with was not colonized with these bacteria after 28 days as shown by quantitative polymerase chain reaction. Protection in this group was associated with an increased number of myeloid precursors in the bone marrow and enhanced macrophage infiltration in the gastric tissue. The bone marrow-derived macrophages from this group showed enhanced phagocytic activity, whereas in animals inoculated only with , this activity was negatively modulated. The protective effect of the studied CHI MPs was also associated with increased gastric concentrations of secretory IgA and enhanced splenocyte proliferation.

[CONCLUSIONS] The obtained results indicate the immunomodulatory potential of CHI MPs loaded with BCG to improve innate and adaptive immune mechanisms, facilitating control of infection in the guinea pig model.