Microbial immune suppression mediated by direct engagement of inhibitory Fc receptor

A microbial polysaccharide (glucuronoxylomannan (GXM)) exerts potent immunosuppression by direct engagement to immunoinhibitory receptor FcγRIIB. Activation of FcγRIIB by GXM leads to the recruitment and phosphorylation of SHIP that prevents IκBα activation. The FcγRIIB blockade inhibits GXM-imduced IL-10 production and induces TNF-α secretion. GXM qnenches LPS-induced TNF-α release via FcγRIIB. The addition of mAb to GXM reverses GXM-induced immunosappression by shifting recognition from FcγRIIB to FcγRIIA. These findings indicate a novel mechanism by which microbial products can impair immune function through direct stimulation of an inhibitory receptor. Furthermore, our observations provide a new mechanism for the ability of specific Ab to reverse the immune inhibitory effects of certain microbial products.