The vaccinia virus N1L protein influences cytokine secretion in vitro after infection.

The vaccinia virus N1L ORF encodes a protein that enhances virulence and replication of the virus by an unknown mechanism. It has been studied for its ability to enhance viral replication and dissemination in the brain and more recently has been linked to an immunomodulatory role in which it inhibits the activation of cytokine transcription activators in Toll-like receptor signaling pathways after pathogen recognition. The effect of N1L on the release of cytokines from human primary monocytes was investigated. Secretion of the proinflammatory, antiviral cytokines TNF-alpha, IL-1beta, IFN-alpha, IFN-beta, and the anti-inflammatory cytokine IL-10 was found to be inhibited by the presence of the N1L protein.

Modulation of gamma interferon-induced major histocompatibility complex class II gene expression by Porphyromonas gingivalis membrane vesicles.

Gamma interferon (IFN-gamma)-induced endothelial cells actively participate in initiating immune responses by interacting with CD4(+) T cells via class II major histocompatibility complex (MHC) surface glycoproteins. Previously, Porphyromonas gingivalis membrane vesicles were shown to selectively inhibit IFN-gamma-induced surface expression of HLA-DR molecules by human umbilical cord vascular endothelial cells. In this study, we demonstrated an absence of HLA-DR alpha mRNA from IFN-gamma-induced cells in the presence of P. gingivalis membrane vesicles by using reverse transcriptase-PCR and Southern blotting. Vesicles also prevented transcription of the gene encoding class II transactivator, a transactivator protein required for IFN-gamma-induced expression of MHC class II genes. In addition, the effects of vesicles on IFN-gamma signal transduction involving Jak and Stat proteins were characterized by using immunoprecipitation and Western blot analyses. Jak1 and Jak2 proteins could not be detected in endothelial cells treated with membrane vesicles. Consequently, IFN-gamma-induced phosphorylation of Jak1, Jak2, and Stat1 alpha proteins was prevented. The class II-inhibitory effect of the membrane vesicles could be eliminated by heating vesicles at 100 degrees C for 30 min or by treating them with a cysteine proteinase inhibitor. This indicates that the cysteine proteinases were most likely responsible for the absence of Jak proteins observed in vesicle-treated cells. The observed increased binding of radiolabeled IFN-gamma to vesicle-treated cells suggests that vesicles may also modulate the IFN-gamma interactions with the cell surface. However, no evidence was obtained demonstrating that vesicles affected the expression of IFN-gamma receptors. Thus, P. gingivalis membrane vesicles apparently inhibited IFN-gamma-induced MHC class II by disrupting the IFN-gamma signaling transduction pathway. Vesicle-inhibited class II expression also occurred in other IFN-gamma-inducible cells. This suggested that the ability of P. gingivalis membrane vesicles to modulate antigen presentation by key cells may be an important mechanism used by this particular bacterium to escape immunosurveillance, thereby favoring its colonization and invasion of host tissues.