Previous studies showed that local macrophages phagocytose nonantigenic
chitin particles (1-10 micrometer
polymers of N-acetyl-<cmd SC>d<cmd /SC> -
glucosamine) through
mannose receptors and produce
IL-12,
IL-18, and
TNF-alpha. These
cytokines lead to the production of IFN-gamma by NK cells. To determine whether
chitin could down-regulate Th2 responses,
chitin was given orally (8 mg/day for 3 days before and 13 days during ragweed
allergen immunization) in BALB/c and C57BL/6 mice. These ragweed-immunized mice were given ragweed intratracheally on day 11. Three days after the challenge, the immunized mice with saline (controls) showed increases in serum
IgE levels and lung eosinophil numbers. The
chitin treatment resulted in decreases of these events in both strains. To dissect the inhibitory mechanisms of Th2 responses, spleen cells (4 x 106 cells/ml) isolated from the ragweed-immunized mice (controls) were cultured in the presence of ragweed and/or
chitin for 3 days (recall responses). Ragweed alone stimulated the production of
IL-4 (0.6 ng/ml),
IL-5 (20 U/ml), and
IL-10 (3.2 ng/ml), but not IFN-gamma. Ragweed/
chitin stimulation resulted in significant decreases of
IL-4,
IL-5, and
IL-10 levels and the production of IFN-gamma (48 U/ml). Moreover, spleen cells isolated from the
chitin-treated mice showed ragweed-stimulated IFN-gamma production (15 U/ml) and significantly lower levels of the Th2
cytokines, suggesting that the immune responses were redirected toward a Th1 response. Collectively, these results indicate that
chitin-induced innate immune responses down-regulate Th2-facilitated
IgE production and lung
eosinophilia in the allergic mouse.