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 between the recovery of intracellular S. typhimurium from PMNs and the presence or absence of the virulence plasmid, or the strains' mouse virulence level. When the oxygen-dependent response of PMNs upon phagocytosis of S. typhimurium was examined by checking the intracellular reduction of nitroblue tetrazolium (NBT), the fraction of PMNs that reduced NBT on phagocytosis of the three strains was around 80%, whereas it was 58% with Escherichia coli, 95% with phorbol 12-myristate 13-acetate and 15% with a negative control. Thus there were no significant differences among the three Salmonella strains in terms of their ability to induce the oxidative response in PMNs. Microscopic analysis of Salmonella-infected PMNs indicated that the intracellular Salmonella induced lysis of PMNs. Both OU5043 and OU5048 exhibited a significant intracellular cytotoxic effect on PMNs after 24 hr of infection and this effect was not associated with the presence or absence of the virulence plasmid. On the other hand, lysis of PMNs was related to the intracellular survival of Salmnonella, as ofloxacin, an antibiotic, appeared to be able to protect human PMNs from Salmonella-induced cytotoxicity when this agent was added into the medium to inactivate the intracellular organism. The ability to induce lysis of PMNs by either wild-type or plasmid-cured strains of S. typhimurium may play a crucial role in the pathogenesis of non-typhoid Salmonella. The contribution of pSTV to human salmonellosis is likely to be limited. Furthermore, early institution of antibiotics with a high intracellular activity against Salmonella, such as fluoroquinolones, may be useful to prevent the dissemination of Salmonella infection.
Chiu
C H
CH
Department of Medicine, Chang Gung Children's Hospital, Taoyuan, Taiwan. cchiu@wpog.childhosp.bc.ca
Ou
J T
JT
D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology*; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D015242:Ofloxacin / Q000494:pharmacology; D010084:Oxidation-Reduction; D010587:Phagocytosis; D010957:Plasmids / Q000235:genetics*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence
D000890:Anti-Infective Agents; D009580:Nitroblue Tetrazolium; D015242:Ofloxacin