4.4 Article

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

Journal

INFECTION AND IMMUNITY
Volume 89, Issue 5, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00786-20

Keywords

chlamydia; active hexose-correlated compound; cold-induced stress

Funding

  1. NIH [1R15AI124156-01]
  2. Center for Natural Products Research of the WV-INBRE under NIH [P20GM103434]

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The study showed that oral feeding of AHCC in stressed mice reduced shedding of C. muridarum, decreased plasma catecholamines, promoted immune cell activation and cytokine production, and enhanced clearance of C. muridarum infection in the murine stress model.
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 in reducing the organ load and changing 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 protective immune function and reduces susceptibility to C. muridarum genital infection. The 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 CDC T cells, increased production of interleukin-12 (IL-12) and interferon gamma (IFN-gamma) and reduced production of IL-4 in CD4(+) T cells, and enhanced expression of surface markers and costimulatory molecules of CD4(+) T cells, bone marrow-derived dendritic cells (BMDCs), and natural killer cells. Coculturing of mature BMDCs with splenic CD4(+) T cells led to the increased and decreased production of T helper 1 and T helper 2 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.

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