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Quantitative and qualitative differences in bronchoalveolar inflammatory cells in Pseudomonas aeruginosa-resistant
K Sapru1, P K Stotland, M M Stevenson
1Centre for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada.
Abstract:
The difference in severity of Pseudomonas aeruginosa-induced chronic lung infection may be determined by differences in host inflammatory responses. In the present study we investigate this possibility using BALB/c and C57Bl/6 mice, resistant and susceptible, respectively, to chronic lung infection with P. aeruginosa. Following intratracheal inoculation of P. aeruginosa-impregnated agar beads, C57Bl/6 mice mounted a stronger inflammatory response with significantly higher total cell numbers in the bronchoalveolar lavage fluid compared with BALB/c mice. While polymorphonuclear leucocytes were the predominant cell in C57Bl/6 mice, macrophages constituted the majority in BALB/c mice at day 7 post-infection. Alveolar macrophages from C57Bl/6 mice showed significantly higher spontaneous production of nitric oxide (NO) at day 7 post-infection compared with BALB/c mice. Following in vitro stimulation with heat-killed Pseudomonas antigen, these cells produced significantly higher NO compared with cells from BALB/c mice at day 21 post-infection. Production of tumour necrosis factor-alpha (TNF-alpha) by alveolar macrophages was significantly higher at day 7 in BALB/c mice compared with C57Bl/6 mice, which showed significantly higher levels at day 28 post-infection. Taken together, these results suggest that defects in the host inflammatory process contribute to the variable outcome of chronic lung infection with P. aeruginosa. An exaggerated inflammatory response dominated by polymorphonuclear cells correlates with susceptibility to infection, whilst a modest inflammatory response dominated by macrophages correlates with resistance. Moreover, the quantity and timing of production of NO and TNF-alpha by alveolar macrophages may modulate the course and outcome of infection.
Insights
Host inflammatory responses influence Pseudomonas aeruginosa lung infection severity. Susceptible mice show exaggerated polymorphonuclear cell responses, while resistant mice exhibit modest macrophage responses and higher nitric oxide production.
Area of Science:
- Immunology
- Microbiology
- Pulmonary Medicine
Background:
- Pseudomonas aeruginosa is a significant cause of chronic lung infections.
- Variability in infection severity suggests a role for host immune responses.
Purpose of the Study:
- To investigate the role of host inflammatory responses in P. aeruginosa-induced chronic lung infection severity.
- To compare the inflammatory profiles of resistant (BALB/c) and susceptible (C57Bl/6) mouse strains.
Main Methods:
- Intratracheal inoculation of P. aeruginosa-impregnated agar beads in BALB/c and C57Bl/6 mice.
- Analysis of bronchoalveolar lavage fluid cell counts and differential counts.
- Measurement of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production by alveolar macrophages.
Main Results:
- C57Bl/6 mice exhibited a stronger inflammatory response with higher cell counts compared to BALB/c mice.
- Polymorphonuclear leukocytes predominated in susceptible C57Bl/6 mice, while macrophages were dominant in resistant BALB/c mice at day 7.
- Alveolar macrophages from C57Bl/6 mice produced significantly higher nitric oxide (NO) spontaneously and after stimulation.
- Tumor necrosis factor-alpha (TNF-alpha) production kinetics differed between strains, with higher early levels in BALB/c mice and later levels in C57Bl/6 mice.
Conclusions:
- Defects in host inflammatory processes contribute to variable outcomes in chronic P. aeruginosa lung infections.
- Exaggerated polymorphonuclear cell-driven inflammation correlates with susceptibility.
- Modest macrophage-driven inflammation, coupled with specific NO and TNF-alpha production patterns, correlates with resistance.