Lentinan treatment of Plasmodium yoelii-infected mice induces apoptosis of regulatory T cells

Abstract

To determine the immunomodulatory effects of lentinan, particularly on immune-suppressing regulatory T cells (Treg), in a mouse model of malaria, BALB/c mice were infected with Plasmodium yoelii by intraperitoneal (i.p.) injection of 1 × 10⁶ red blood cells containing Py17XL, and the infected mice were randomized into either a control group for i.p. injection of PBS or an experiment group for i.p. injection of lentinan. The results show that mean survival was significantly longer for infected mice treated with lentinan (8.10 ± 2.53 days) than for infected controls treated with PBS (5.20 ± 1.20 days; P<0.01). Further, IL-12 and IFN-γ expression in spleen cells were significantly higher in the experiment group than the control group (P<0.01). When Treg cells were isolated by CD antibody  detection from peripheral blood, a higher proportions were undergoing apoptosis in the experiment group than those in the control group (P<0.001). To determine the mechanism of cell death in Tregs, we analyzed Bax and Bcl-2 expression. Bax was detected at significantly higher levels, while Bcl-2 was significantly lower in Treg cells from lentinan-treated animals (P<0.001). In conclusion, lentinan significantly delayed progression of P. yoelii infection in mice by up-regulating anti-inflammatory cytokines and triggering apoptosis of Treg cells through up-regulation of Bax and down-regulation of Bcl-2, and which should be suggested in the clinical experience in the future.

Key words: Lentinan, Plasmodium yoelii, regulatory T cells, apoptosis.