Active Hexose-Correlated Compound Restores Gene Expression and Protein Secretion of Protective Cytokines of Immune Cells in a Murine Stress Model during Chlamydia muridarum Genital Infection

Abstract

Chlamydia trachomatis genital infection is the most common bacterial sexually transmitted disease worldwide. Previously we reported that cold-induced stress results in immune suppression of mice that subsequently leads to increased intensity of Chlamydia muridarum genital infection. Furthermore, we demonstrated that stressed mice orally fed with active hexose correlated compound (AHCC) have reduced shedding of C. muridarum from the genital tract. However, the mechanism of AHCC on reducing the organ load and changes in the immune response in the stress model is not well known. This study evaluated infection and changes in immunological parameters of stressed AHCC-fed mice with or without C. muridarum genital infection. We hypothesized that AHCC feeding to stressed mice restores the protective immune function and reduces susceptibility to C. muridarum genital infection. Results show that oral feeding of stressed mice with AHCC resulted in decreased shedding of C. muridarum from the genital tract, reduced production of plasma catecholamines, increased expression of T-bet and reduced GATA-3 in CD4+ T cells, increased production of IL-12 and IFN-γ, and reduced production of IL-4 in CD4+ T cells, and enhanced expression of surface markers and co-stimulatory molecules of CD4+ T cells, bone marrow-derived dendritic cells (BMDCs), and natural killer cells. Co-culturing of mature BMDCs with splenic CD4+ T cells led to the increased and decreased production of T-helper 1 and T-helper2 cytokines, respectively. Overall, our results show that AHCC fosters the restoration of Th1 cytokine production while reducing Th2 cytokine production, which would promote C. muridarum clearance in the murine stress model.