Early induction of antibacterial activities distinguishes response of mice to infection with non-permissive from response to permissive Salmonella

Abstract

Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid in humans, shares very high homology with closely related serovar, S. Typhimurium. Yet, unlike S. Typhimurium, S. Typhi does not establish infection in mice, the reasons for which are not well understood. Here, we present evidence that unlike S. Typhimurium, S. Typhi brings about induction of extracellular and intracellular antibacterial activities in mice. Cell-free peritoneal fluids from S. Typhi but not S. Typhimurium-infected mice inhibited replication of Salmonella ex vivo. The production of this activity was reduced in presence of serine protease inhibitor, phenylmethylsulfonlyl fluoride (PMSF). PMSF also inhibited generation of antibacterial activity released from in vitro S. Typhi - infected peritoneal macrophages in a cell death - dependent manner. Intracellularly, infection with S. Typhi in vitro as well as in vivo resulted in increased mRNA levels of iron-regulating molecules, ferroportin and lipocalin. These results suggest that induction of antibacterial molecules early on in mice in response to S. Typhi may prevent establishment of infection with this Salmonella serovar.