Intracellular Salmonella typhimurium induce lysis of human polymorphonuclear leukocytes which is not associated with the Salmonella virulence plasmid

The interaction between Salmonella typhimurium and human polymorphonuclear leukocytes (PMNs) was analyzed in vitro. Three S. typhimurium strains, the wild-type strain OU5043, its isogenic virulence plasmid-cured strain OU5048 , and LT2, which represented the types that exhibited three mouse virulence levels, respectively, were used in this study. There was no correlation be tween the recovery of intracellular S. typhimurium from PMNs and the presen ce or absence of the virulence plasmid, or the strains' mouse virulence lev el. When the oxygen-dependent response of PMNs upon phagocytosis of S, typh imurium was examined by checking the intracellular reduction of nitroblue t etrazolium (NBT), the fraction of PMNs that reduced NET on phagocytosis of the three strains was around 80%, whereas it was 58% with Escherichia:a col i, 95% with phorbol 12-myristate 13-acetate and 15% with a negative control , Thus there were no significant differences among the three Salmonella str ains in terms of their ability to induce the oxidative response in PMNs, Mi croscopic analysis of Salmonella-infected PMNs indicated that the intracell ular Salmonella induced lysis of PMNs, Both OU5043 and OU5048 exhibited a s ignificant intracellular cytotoxic effect on PMNs after 24 hr of infection and this effect was not associated with the presence or absence of the viru lence plasmid, On the other hand, lysis of PMNs was related to the intracel lular survival of Salmonella, las ofloxacin, an antibiotic, appeared to be able to protect human PMNs from Salmonella-induced cytotoxicity when this a gent was added into the medium to inactivate the intracellular organism, Th e ability to induce lysis of PMNs by either wild-type or plasmid-cured stra ins of S, typhimurium may play a crucial role in the pathogenesis of non-ty phoid Salmonella. The contribution of pSTV to humam salmonellosis is likely to be limited. Furthermore, early institution of antibiotics,vith a high i ntracellular activity against Salmonella, such as fluoroquinolones, may be useful to prevent the dissemination of Salmonella infection.