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BCG-induced susceptibility of mice to challenge with Pseudomonas aeruginosa
Abstract:
Mice infected with Mycobacterium bovis, BCG, were shown to be highly susceptible to subsequent challenge with Pseudomonas aeruginosa. The susceptibility was characterized by the enhanced mortality and shortened survival after challenge with P. aeruginosa. BCG-treated mice did not show any enhanced susceptibility to challenge with Gram-positive bacteria such as Staphylococcus aureus or Listeria monocytogenes. BCG-treated mice eliminated P. aeruginosa from their organs in a pattern similar to that in untreated mice. There was no significant difference in the bactericidal activities of polymorphonuclear cells and macrophages between BCG-treated and untreated mice. An equal amount of endotoxin was detected by the Limulus lysate assay in the blood of both BCG-treated and untreated mice after challenge with P. aeruginosa. The enhanced susceptibility induced by BCG pretreatment could be decreased when the mice were rendered LPS-tolerant by injections of small amounts of LPS. These results suggest that BCG-induced susceptibility to P. aeruginosa can be ascribed to an enhanced susceptibility to the lethal effect of LPS produced by challenge bacteria, and not to the impairment of the ability to eliminate infected bacteria.
Insights
Mycobacterium bovis, bacille Calmette-Guérin (BCG), infection increases susceptibility to Pseudomonas aeruginosa. This heightened susceptibility is due to an increased response to bacterial lipopolysaccharide (LPS), not impaired bacterial clearance.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Mycobacterium bovis bacille Calmette-Guérin (BCG) is a live attenuated strain used as a vaccine.
- BCG vaccination can modulate immune responses, potentially affecting susceptibility to secondary infections.
Purpose of the Study:
- To investigate the effect of BCG pretreatment on the susceptibility of mice to subsequent challenge with Pseudomonas aeruginosa.
- To elucidate the mechanisms underlying BCG-induced susceptibility to P. aeruginosa.
Main Methods:
- Mice were pretreated with BCG and subsequently challenged with P. aeruginosa, Staphylococcus aureus, or Listeria monocytogenes.
- Bacterial load in organs, survival rates, and immune cell activity were assessed.
- Lipopolysaccharide (LPS) tolerance was induced to evaluate its effect on susceptibility.
Main Results:
- BCG-treated mice exhibited significantly increased mortality and reduced survival after P. aeruginosa challenge, but not after challenge with Gram-positive bacteria.
- No differences were observed in bacterial clearance or the bactericidal activity of immune cells between BCG-treated and control mice.
- Induced LPS tolerance reduced the enhanced susceptibility to P. aeruginosa in BCG-pretreated mice.
Conclusions:
- BCG pretreatment confers susceptibility to P. aeruginosa, primarily by increasing sensitivity to the lethal effects of bacterial lipopolysaccharide (LPS).
- The observed susceptibility is not due to impaired bacterial elimination by immune cells.