Interferon induction and augmentation of natural-killer activity by Staphylococcus protein A

Abstract

Protein A from Staphylococcus aureus (SpA)-induced interferon (IF) production and augmented natural-killer (NK) activity in human peripheral blood mononuclear cells (PBL). IF production was apparent 8 hr and peaked 24 hr after exposure to SpA. Augmentation of NK activity occurred within 10 hr of IF production with peak NK activity occurring 48 hr after exposure to SpA. SpA-induced augmentation of NK activity correlated directly with IF production ( r = 0.997; P < 0.005). Supernatants from SpA-induced PBL cultures also enhanced NK activity. Pretreatment of these supernatants with antileukocyte (Type I) IF serum had no effect on either their ability to augment NK activity or their antiviral (IF) activity. Both the NK-augmenting and antiviral activity of such supernatants were abrogated by trypsin digestion, heat inactivation (56 °C for 1 hr) and treatment at pH 2 for 48 hr, suggesting that Type II IF was induced by SpA. Furthermore, the kinetics of development of antiviral activity in human fibroblast cultures by SpA-induced IF followed the pattern characteristic of Type II IF. Cell-fractionation studies showed that SpA-induced IF production was depressed in macrophage-enriched PBL and increased in nonadherent PBL. Moreover, depletion of Fcreceptor-positive (FcR+) lymphocytes with IgG-coated bovine erythrocytes before SpA treatment abrogated IF production and augmentation of NK activity. Taken together, these data suggest that SpA induces human nonadherent, FcR+ PBL to produce Type II IF, which augments NK activity against several cultured target cell lines.