SYSTEMIC INFECTION OF MICE BY WILD-TYPE BUT NOT SPV(-) SALMONELLA-TYPHIMURIUM IS ENHANCED BY NEUTRALIZATION OF GAMMA-INTERFERON AND TUMOR-NECROSIS-FACTOR-ALPHA

The spy genes of the virulence plasmid of Salmonella typhimurium and o ther nontyphoidal serovars of S. enterica are involved in systemic inf ection by increasing the replication rate of the bacteria in host tiss ues beyond the intestines. We considered the possibility that the Spy virulence function is to evade suppression by the host response to inf ection. To examine this possibility, gamma interferon (IFN-gamma) and/ or tumor necrosis factor alpha (TNF-alpha) were neutralized in BALB/c mice by intraperitoneal administration of monoclonal antibodies. Neutr alization of IFN-gamma and/or TNF-alpha resulted in increased splenic infection with wild-type salmonellae after oral inoculation; however, Spv(-) salmonellae were defective at increasing splenic infection in c ytokine-depleted mice. The use of a temperature-sensitive marker plasm id, pHSG422, indicated that neutralization of IFN-gamma caused less ki lling of wild-type S. typhimurium, while neutralization of TNF-alpha r esulted in an increased in vivo replication rate for wild-type salmone llae. These results demonstrate that the Spy virulence function is not to evade suppression of bacterial infection normally mediated by IFN- gamma or TNF-alpha.