The immunomodulatory properties of Cordyceps cicadae on resting and proliferating human T-lymphocytes

Abstract

Cordyceps cicadae, a parasitic fungus, has been used as a traditional Chinese herb for treatment of illnesses related to immune dysfunction. However, mechanistic actions are not entirely clear. The specific aim of the present study is to investigate the immunological mechanisms of C. cicadae on human T lymphocytes in vitro. The two main objectives carried out in the present study in order to achieve the aim are: i. to investigate the immunological effects of the water extract of C.cicadae on human resting and proliferating T lymphocytes; 2. to investigate the adjuvant property of C.cicadae with the immunosuppressant Cyclosporin A (CsA) on the control of human T cells proliferation, cell death and cytokines secretion.

C. cicadae has demonstrated a dual effect of enhancing the activity of resting Tlymphocytes and inhibiting that of PHA-stimulated cells. In resting T cells, C. cicadae increased cell activity, cytokines secretion, expression of IL-2α receptor (CD25) and the population of Th17 as well as Treg cells without affecting the cell cycle progression. In the viability and cell death test, C. cicadae has been found not to exert toxicity on T cells. These results reveal the role of C. cicadae as an invigorant to improve the immunity as a whole in healthy individuals.

In PHA-stimulated proliferating T-lymphocytes, C. cicadae inhibited the cell proliferation by arresting them at G0/G1 phase and decreasing both S and G2/M phase cell populations. The inhibitory effect was not through the induction of cell death as both PHA- and CsA-induced cell apoptosis and necrosis were reduced by C. cicadae treatment. It was believed that C. cicadae affects the progression of inflammatory responses by selectively suppressing the secretion of Th1 cytokines and enhancing that of Th2 cytokines, but it seemed unable to influence the CD25 expression in PHA- and CsA-treated T cells. An increased population of Treg cells by C. cicadae was also observed in PHA-stimulated T cells.

C. cicadae adjuvant to CsA showed greater inhibition of cell proliferation and Th1 cytokines production. However, C. cicadae antagonized the effect of CsA in the secretion of IL-10, a Th2 and Treg cytokine. These results suggest a potential role of C. cicadae as an adjuvantive agent with CsA in the therapy of autoimmune diseases and organ transplantation. Furthermore, C. cicadae demonstrated superior immunomodulatory properties over CsA as it can act selectively between resting and proliferating T cells, and also protect them from apoptosis and necrosis, alleviating the toxic effect caused by CsA. In summary, this study showed the potential of C. cicadae as an immunomodulator from which both healthy individuals and inflammatory disease patients can benefit.