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 contribute to respiratory immunopathology. We therefore investigated in vitro the interaction between chlamydiae and macrophages with cocultures of C. pneumoniae and AM from 12 healthy volunteers. Inflammatory responses were evaluated through lucigenin-amplified chemiluminescence; secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin 8 (IL-8); and expression of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen-DR (HLA-DR). C. pneumoniae readily induced productive 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. pneumoniae pneumonia. AM responded to the infection with a marked, dose-dependent release of reactive oxygen species, TNF-alpha, IL-1beta, and IL-8. ICAM-1 expression remained unchanged, but HLA-DR was significantly upregulated. Our data indicate that the release of antimicrobial mediators cannot prevent chlamydial infection and replication in AM, but may be involved in amplification of the local inflammatory response in C. pneumoniae pneumonia.
Redecke
V
V
Department of Medicine II and Institute of Medical Microbiology, Medical University of Lübeck, Lübeck, Germany.
Dalhoff
K
K
Bohnet
S
S
Braun
J
J
Maass
M
M
D000328:Adult; D002452:Cell Count / Q000187:drug effects; D016993:Chlamydophila pneumoniae / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007239:Infections / Q000382:microbiology*; D007249:Inflammation / Q000382:microbiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008163:Luminescent Measurements; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D010587:Phagocytosis / Q000502:physiology; D011112:Polymyxin B / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006684:HLA-DR Antigens; D007378:Interleukins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D006493:Heparin; D011112:Polymyxin B