Outer membrane vesicles of Porphyromonas gingivalis inhibit IFN-gamma-mediated MHC class II expression by human...

Porphyromonas gingivalis is thought to be one of the major pathogenic organisms of adult periodontitis. Of the several virulence factors associated with the pathology it causes, evidence is now presented suggesting that outer membrane vesicles, which form from blebbing of the outer membrane, may also contribute to the pathogenesis of this bacterium. To evaluate this possibility, outer membrane vesicles were isolated from cultures of P. gingivalis and tested for their ability to promote inflammation and for their effects on the biosynthesis of E-selectin and ICAM-1 adhesion molecules and MHC class II glycoproteins. The results indicate that these vesicles are capable of inducing acute inflammation characterized by the accumulation of a large number of neutrophils in the connective tissue. This cellular response corresponds to the vesicle-mediated biosynthesis and surface membrane expression of E-selectin and ICAM-1 by vascular endothelial cells. In contrast, IFN-gamma-dependent synthesis of MHC class II molecules was found to be inhibited by vesicles. Inhibition of HLA-DR expression occurred regardless of whether vesicles were added at the same time as, 24 h before, or 24 h after IFN-gamma stimulation of endothelial cells, suggesting that the inhibitory effects occur at both the membrane and intracellular level. These findings, taken together, indicate that P. gingivalis membrane vesicles are capable of inducing and regulating cellular responses involved in inflammation and initiation of acquired immunity. Membrane vesicles are composed of muramyl peptides, periplasmic proteins and outer membrane constituents. The combination of these components probably contribute to the immune regulatory functions reported herein.