Diminished immune response to vaccinations in obesity: Role of myeloid-derived suppressor and other myeloid cells

Abstract

Obesity is a chronic inflammatory condition associated with an increased production of cytokines and exacerbated immune response. However, obese subjects are susceptible to infections and respond poorly to vaccines. This study evaluated the immune responses of obese mice and the underlying mechanisms by exploring the roles of myeloid cells. Diet-induced obese (DIO) mice were prepared from C57BL/6J mice fed a high-calorie and high-fat diet for 12 weeks. Humoral and cellular immune responses of DIO mice to a hepatitis B vaccine containing the hepatitis B surface antigen (HBsAg) were assessed in sera and via a lymphoproliferative assay, respectively. The effects of CD11b(+)GR1(+) myeloid-derived suppressor cells (MDSC) and CD11b(+)GR1(-) non-MDSC on T cell proliferation and cytokine production were compared via a cell culture system. The production of cytokines, expression of activation and exhaustion markers, and proportions of apoptotic T cells were estimated with flow cytometry. Increased T and B lymphocyte proliferation and higher interferon-γ and tumor necrosis factor-α levels were detected in spleen cells and liver non-parenchymal cell cultures of DIO mice compared to controls (p<0.05). However, antibody to HBsAg (anti-HBs) levels and HBsAg-specific T cell proliferation were significantly lower in DIO mice compared to controls (p<0.05). The addition of MDSC, but not non-MDSC, induced a decrease in HBsAg-specific T cell proliferation, lower cytokine production, decrease in T cell activation, and increase in T cell exhaustion and apoptosis (p<0.05). MDSC play an important role in mediating impaired antigen-specific immunity.