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Pseudomonas aeruginosa clearance in mice: comparison of tissue, strain, and corticosteroid effects
Abstract:
We used a murine model to determine whether chronic corticosteroid therapy has uniform effects on bacterial clearance processes in different tissues. After a 2-week regimen of oral prednisolone, Swiss Webster mice were challenged with Pseudomonas aeruginosa strain PAO1 or virulent derivatives of PAO1 (IP-8 and IT-10). Chronic corticosteroid therapy delayed the clearance of strain PAO1 from the peritoneal cavity. However, steroid treatment did not reduce the neutrophil influx, did not reduce the in vivo phagocytic capacity of neutrophils, and did not alter bactericidal activity of peritoneal exudate cells in vitro. Virulent isolates (IP-8 and IT-10) replicated in the peritoneal cavity in steroid-treated mice even though the neutrophil influx was similar to control mice. In contrast to the abnormal peritoneal clearance, all strains were rapidly cleared from the lungs of control and steroid-treated mice after aerosol challenge. Neutrophil influx into bronchoalveolar spaces was greater in steroid-treated mice than in control mice. All mice (control and steroid treated) survived these challenges, except for some steroid-treated mice infected intraperitoneally with IP-8. These results demonstrate that chronic steroid therapy alters bacterial clearance processes on the peritoneal surfaces to a greater extent than in the lower respiratory tract. The explanation for this altered clearance in the peritoneum is unclear, but cannot be explained by reductions in neutrophil migration to inflammatory stimuli. Therefore, the infectious risk associated with chronic corticosteroid therapy appears to depend on both the tissue and the virulence of the bacterial strain and may reflect alterations in clearance processes other than neutrophil migration.
Insights
Chronic corticosteroid therapy impairs bacterial clearance in mouse peritoneal cavities but not lungs. This suggests tissue-specific effects on immune response and infection risk, independent of neutrophil function.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Corticosteroids are widely used to suppress inflammation.
- Their impact on host defense mechanisms, particularly bacterial clearance, requires detailed investigation.
- Tissue-specific effects of corticosteroid therapy on immunity are not fully understood.
Purpose of the Study:
- To investigate the effects of chronic corticosteroid therapy on bacterial clearance in different murine tissues.
- To determine if corticosteroid treatment uniformly affects bacterial clearance processes.
- To explore the relationship between corticosteroid therapy, bacterial virulence, and tissue-specific immune responses.
Main Methods:
- Murine model using Swiss Webster mice treated with oral prednisolone.
- Challenge with Pseudomonas aeruginosa strains (PAO1, IP-8, IT-10) via intraperitoneal injection or aerosol inhalation.
- Assessment of bacterial clearance, neutrophil influx, phagocytic capacity, and bactericidal activity in peritoneal cavity and lungs.
Main Results:
- Chronic corticosteroid therapy delayed Pseudomonas aeruginosa clearance from the peritoneal cavity.
- Steroid treatment did not impair neutrophil influx, in vivo phagocytosis, or in vitro bactericidal activity.
- Virulent bacterial strains replicated in the peritoneal cavity of steroid-treated mice.
- All bacterial strains were rapidly cleared from the lungs of both control and steroid-treated mice.
- Neutrophil influx was higher in the lungs of steroid-treated mice.
Conclusions:
- Chronic corticosteroid therapy significantly alters bacterial clearance in the peritoneal cavity but not the lungs.
- The observed impairment in peritoneal clearance is not attributable to reduced neutrophil migration or function.
- Infectious risk associated with corticosteroid use is tissue-dependent and influenced by bacterial virulence, potentially involving mechanisms beyond neutrophil activity.