Chitin particle-induced cell-mediated immunity is inhibited by soluble mannan: mannose receptor-mediated phagocytosis initiates IL-12 production.

Previous studies showed that mouse spleen cells produced IL-12, TNF-alpha, and IFN-gamma when stimulated with phagocytosable-size chitin particles (N-acetyl-D-glucosamine polymers). To dissect the mechanisms of the cytokine production in this study, spleen cells from BALB/c mice were cultured with 1 to 10 microm chitin particles, heat-killed Corynebacterium parvum vaccine, zymosan, and mannan (a mannose polymer)-coated latex beads (1 microm) at 1, 10, or 100 microg/ml. We found that these particles induced IL-12, TNF-alpha, and IFN-gamma. However, these cytokines were not produced when spleen cells were cultured with soluble chitin, mannan, or laminarin (a polymer of beta-glucan), 1 to 10 microm beta-glucan particles, laminarin-coated latex beads, 1 microm latex beads, 50 to 100 microm chitin particles, or 50 to 100 microm mannan-coated beads. Soluble mannan, but not soluble laminarin, inhibited cytokine production following stimulation with 1 to 10 microm chitin particles, zymosan, or heat-killed C. parvum. In addition, cytochalasin D also inhibited cytokine production. The treatments with soluble mannan or with cytochalasin D, in sharp contrast, did not inhibit LPS-induced IL-12/IFN-gamma production or exogenous IL-12-induced IFN-gamma production. Finally, spleen cells from C3H/HeJ mice also showed comparable levels of IL-12/TNF-alpha/IFN-gamma production when induced by 1 to 10 microm chitin particles. Taken together, our results indicate that mannose receptor-mediated phagocytosis, but not the receptor-mediated pinocytosis, is highly associated with the production of IFN-gamma-inducing extracellular signaling factors such as IL-12 and TNF-alpha. The novel mechanism of phagocytosis-dependent IL-12 production appears to be distinct from that of LPS-induced cytokine production.