Interaction of Chlamydia pneumoniae and human alveolar macrophages: Infection and inflammatory response

The obligate intracellular pathogen Chlamydia pneumoniae is associated with chronic respiratory, atherosclerotic, and rheumatic disease. The alveolar macrophage (AM) is a potential target cell for the pathogen and may contrib ute to respiratory immunopathology. We therefore investigated in vitro the interaction between chlamydiae and macrophages with cocultures of C. pneumo niae and AM from 12 healthy volunteers. Inflammatory responses were evaluat ed through lucigenin-amplified chemiluminescence; secretion of tumor necros is factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleuki n 8 (1L-8); and expression of intercellular adhesion molecule-1 (ICAM-1) an d human leukocyte antigen-DR (HLA-DR). C. pneumoniae readily induced produc tive infection in the AM. Inclusions containing replicating pathogens could be maintained for up to 120 h. Morphologically similar infection patterns were seen ex vivo in AM collected from six patients with known C. pneumonia e pneumonia. AM responded to the infection with a marked, dose-dependent re lease of reactive oxygen species, TNF-alpha, IL-1 beta, and IL-8. ICAM-1 ex pression remained unchanged, but HLA-DR was significantly upregulated. Our data indicate that the release of antimicrobial mediators cannot prevent ch lamydial infection and replication in AM, but may be involved in amplificat ion of the local inflammatory response in C. pneumoniae pneumonia.