Pneumocystis carinii Major Surface Glycoprotein Dampens Macrophage Inflammatory Responses to Fungal β-glucan.

Pneumocystis Major Surface Glycoprotein (Msg) is a 120-kD surface protein complex on the organism with importance in adhesion and immune recognition. Herein, we show that Msg significantly impairs Tumor Necrosis Factor alpha (TNF-alpha) secretion by macrophages induced by Saccharomyces cerevisiae (Sc) and Pneumocystis carinii (Pc) β-glucans. Msg was shown to greatly reduce β-glucan-induced Dectin-1 ITAM phosphorylation. Msg also down regulated Dectin-1 receptor mRNA expression in the macrophages. Interestingly, Msg incubation with macrophages resulted in significant mRNA upregulation of both CLR receptors Mincle and MCL in Msg protein presence alone but to even greater amounts in the presence of Pc β-glucan. Lastly, the silencing of MCL and Mincle resulted in TNF-alpha secretions similar to that of macrophages treated with Pneumocystis β-glucan alone, suggestive of an inhibitory role for these two CLRs in Msg suppressive effects on host cell immune response. Taken together, these data indicate the Pneumocystis Msg surface protein complex can act to suppress host macrophage inflammatory responses to the proinflammatory β-glucan components of the organisms.