Under the hypercapnic challenge: how macrophages react to pneumonia-causing bacteria

<bold>Objective:</bold> To evaluate the inflammatory response of macrophage-like THP-1 as a result of infection with <italic>Pseudomonas aeruginosa</italic> (PA) or <italic>Streptococcus pneumoniae</italic> (SP) under different CO₂ concentrations, and determine the impact of macrophage response in bacterial survival. <bold>Methods:</bold> Cultures of macrophage-like THP-1 cells were separately infected with PA or SP for 1h at 37°C under normocapnic (5% CO₂) or hypercapnic (15% CO₂) conditions. Extracellular and intracellular bacterial survival post-infection was evaluated through seeding in blood agar plates. 24h after infection, at 37ºC and 5% or 15% CO₂, cell culture supernatant was analysed through ELISA technique for inflammatory cytokines (IL-1β, IFN-γ, CCL-2, IL-8 and IL-10). <bold>Results:</bold> Under hypercapnic conditions, IL-1β secretion is enhanced in both infections, IL-10 decreases only in PA infection and chemokines are decreased (Fig 1A-E). In PA-infected macrophages the secretion of chemokines is inhibited, in SP infection macrophages could play a pivotal role as recruiters (Fig 1D-E). No differences in post-infection bacterial extracellular survival were determined (Fig 1F). PA could be establishing intracellular niches within macrophages since intracellular growth is detected 24h post-infection (Fig 1G). <fig><object-id>erj;64/suppl_68/PA5323/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <bold>Conclusion:</bold> Macrophages perform different defensive responses against PA and SP infection. Hypercapnic condition on bacterial-infection response could play a detrimental role.