LETHAL SYNERGISM BETWEEN INFLUENZA INFECTION AND STAPHYLOCOCCAL-ENTEROTOXIN-B IN MICE

Superantigen hyperactivation of the immune system has variable, someti mes lethal consequences for the host, Here we show that concurrent inf luenza infection enhanced the effects of the bacterial superantigen st aphylococcal enterotoxin B (SEB) in mice. The effect was T cell-depend ent, and maximal synergism was observed when SEB was administered 7 da ys after the virus, a timepoint during infection associated with high viral titers, a vigorous cytotoxic T cell response, and extensive lung pathology, The influenza infection enhanced the SEB-induced cytokine response in terms of higher absolute levels of cytokine, sustained sec retion, and localization to the respiratory tract, In particular, TNF and IFN-gamma were implicated in the mechanism of death because their neutralization protected the mice from death, and recombinant IFN-gamm a and TNF alpha mimicked the lethal effect of SEB in influenza-infecte d mice, This lethal synergism between concurrent influenza infection a nd superantigen exposure points to the danger of secondary bacterial i nvolvement in viral pneumonia, and suggests mechanisms that may contri bute to sudden and unexpected death from influenza infection, In addit ion, these data demonstrate that the in vivo effects of superantigen e xposure can be strongly influenced by the immune activation status of the host.