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Effect of polyinosinic-polycytidylic acid (pl:C) on experimental mouse salmonellosis
1National Public Health Institute, Helsinki, Finland.
Abstract:
The effect of the non-specific immunomodulator polyinosinic-polycytidylic acid (pl:C) on the resistance to experimental salmonellosis was studied in the mouse. The polynucleotide was unexpectedly found to decrease the innate relative resistance of the mouse to this intracellular infection. pl:C (100 micrograms/mouse) injected 24 h before either intravenous (i.v.) or intraperitoneal (i.p.) challenge resulted in an increased intracellular rate of growth of the Salmonella in the liver, but did not affect the initial extracellular survival of the bacteria in the peritoneal cavity. By contrast, pl:C did not affect the course of mouse peritonitis caused by E. coli O18:K1, which multiplies extracellularly or that of Listeria monocytogenes, which, like Salmonella, grows intracellularly in the liver. The effect of pl:C on salmonellosis could not be explained by production of alpha or beta interferon (IFN) since it could not be demonstrated by injecting purified IFN nor could it be abolished by injecting neutralizing anti-IFN antibodies. Thus, pl:C seems to have a specific effect on salmonellosis by impairing the growth restriction of these bacteria in the liver macrophages.
Insights
The immunomodulator polyinosinic-polycytidylic acid (pl:C) unexpectedly reduced mouse resistance to Salmonella infection. This compound impaired liver macrophage control of intracellular bacterial growth, specifically impacting salmonellosis.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Polyinosinic-polycytidylic acid (pl:C) is a non-specific immunomodulator.
- Salmonellosis is an intracellular infection caused by Salmonella bacteria.
- The innate resistance of mice to intracellular pathogens is a key factor in disease outcome.
Purpose of the Study:
- To investigate the effect of pl:C on experimental salmonellosis in mice.
- To determine if pl:C influences the innate resistance to Salmonella infection.
- To elucidate the mechanism by which pl:C affects Salmonella growth.
Main Methods:
- Mice were injected with pl:C 24 hours before intravenous or intraperitoneal challenge with Salmonella.
- Bacterial growth rates were assessed in the liver and peritoneal cavity.
- The effects of pl:C were compared to its effects on infections with E. coli and Listeria monocytogenes.
- Interferon (IFN) levels and the efficacy of anti-IFN antibodies were evaluated.
Main Results:
- pl:C administration decreased innate resistance to Salmonella, increasing intracellular bacterial growth in the liver.
- pl:C did not affect extracellular survival of Salmonella in the peritoneal cavity.
- pl:C did not alter the course of experimental peritonitis caused by extracellular E. coli or intracellular Listeria monocytogenes.
- The observed effect of pl:C on salmonellosis was independent of alpha or beta interferon production.
Conclusions:
- pl:C specifically impairs the innate resistance of mice to Salmonella infection.
- The mechanism involves impaired growth restriction of Salmonella within liver macrophages.
- This effect is distinct from the general immunomodulatory actions of pl:C and its influence on other intracellular or extracellular bacterial infections.