Immunomodulatory Activity ofLactococcus lactisGCWB1176 in Cyclophosphamide-Induced Immunosuppression Model

Abstract

Recently,Lactococcus lactissubsp.lactishas been reported to have immunostimulating properties in an immunosuppressed-animal model. However, the immunological activities ofLactococcus lactisand the molecular mechanisms remain unclear. In this report, we evaluated the immunostimulating activity and associated mechanisms ofLactococcus lactissubsp.lactisGCWB1176 (GCWB1176) in macrophages and cyclophosphamide (CTX)-induced immunosuppressed mice. In a series of safety tests, GCWB1176 was found to have a negative response to hemolysis, as well as susceptibility to antibiotics. Administration of GCWB1176 elevated natural killer (NK) cell activities; concanavalin A-induced T cell proliferation; and serum levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-10 and IL-12 in CTX-induced immunosuppressed mice. In RAW264.7 macrophages, treatment with GCWB1176 induced phagocytic activity and increased the production of nitric oxide (NO) and expression of inducible NO synthase. Simultaneously, GCWB1176 increased the production of TNF-alpha, IFN-gamma, IL-1 beta, IL-10 and IL-12 from mouse splenocytes and RAW264.7 cells. In addition, GCWB1176 significantly increased the transcriptional activities of NF-kappa B and iNOS. Taken together, GCWB1176 improved immune function through the activation of macrophages and NK cells. These findings suggest that dietary supplementation of GCWB1176 may be used to enhance immunity.