Rhodotorula mucilaginosa ZTHY2 Attenuates Cyclophosphamide-Induced Immunosuppression in Mice

SIMPLE SUMMARY: Rhodotorula mucilaginosa is widely detected in the environment, and it produces broad metabolites such as carotenoid pigments, amino acids, polyunsaturated fatty acids, polysaccharides, and enzymatic substances. We previously isolated a strain of Rhodotorula mucilaginosa ZTHY2 from the coastal waters of the South China Sea, which showed probiotic properties. Rhodotorula mucilaginosa ZTHY2 promoted the growth of experimental animals, increased the abundance of beneficial bacteria in gut, and enhanced immune function. Given that immunosuppression is common in livestock, environmental stresses, such as overpopulation, food contamination, and chronic diseases, contribute to immunosuppression of livestock associated with declining animal production, failed immunoprophylaxis, and economic losses. Therefore, in this study, cyclophosphamide was used to generate immunosuppressed models to further evaluate the immunomodulatory effects of Rhodotorula mucilaginosa ZTHY2. ABSTRACT: Rhodotorula mucilaginosa (R. mucilaginosa) can enhance the immune and antioxidant function of the body. However, whether R. mucilaginosa has an immunoregulatory effect on cyclophosphamide (CTX)-induced immunosuppressed animals remains to be clarified. In this study, the R. mucilaginosa ZTHY2 that we isolated from the coastal waters of the South China Sea previously was prepared in order to investigate its immunoprotective effect on CTX-induced immunosuppression in mice, and the effects were compared to those of Lactobacillus acidophilus (LA) (a well-known probiotic). Seventy-two male SPF mice were divided into six groups: The C group (control); IM group (immunosuppressive model group) (+CTX); Rl, Rm, and Rh groups (+CTX+low, medium, and high concentration of R. mucilaginosa, respectively); and PC (positive control) group (+CTX+LA). After a 28-day feeding trial, blood samples were taken for biochemical and serum immunological analysis, and the thymus and spleen were collected to analyze the organ index, lymphocyte proliferation and differentiation, and antioxidant capacity. The findings showed that R. mucilaginosa ZTHY2 improved the spleen and thymus indices, effectively attenuated immune organ atrophy caused by CTX, and enhanced the proliferation of T and B lymphocytes induced by ConA and LPS. R. mucilaginosa ZTHY2 promoted the secretion of cytokines and immunoglobulins and significantly increased the contents of IL-2, IL-4, IL-6, TNF-α, IFN-γ, IgA, IgG, IgM, CD4, CD8, CD19, and CD20 in serum. The proportion of CD4(+), CD8(+), CD19(+), and CD20(+) lymphocytes in spleen, thymus, and mesenteric lymph nodes were increased. In addition, R. mucilaginosa ZTHY2 reduced the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increased glutathione (GSH), total superoxide dismutase (SOD), and catalase (CAT) levels. Our results indicated that R. mucilaginosa ZTHY2 can significantly enhance the immune function of immunosuppressed mice, and improving antioxidant capacity thus attenuates CTX-induced immunosuppression and immune organ atrophy.