Interaction of Chlamydia pneumoniae and Human Alveolar Macrophages: Infection and Inflammatory Response

Abstract

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.

Imbalanced secretion of IL‐1β and IL‐1RA inChlamydia pneumoniae-infected mononuclear cells from COPD patients

“…In acute exacerbation of COPD, the pulmonary compartment represents a site of localised inflammation, in which AMs play a pivotal role in the host defence against bacterial pathogens [16]. Initially, C. pneumoniae infects AMs, which results in enhanced secretion of the pro-inflammatory cytokines IL-1b and TNF-a [17]. Besides the beneficial effects of proinflammatory cytokine secretion in infectious diseases, some of their biological activities may contribute to structural tissue damage if an adequate anti-inflammatory immune response is lacking [18].…”

“…The pro-inflammatory cytokine secretion pattern of C. pneumoniae-infected AMs and PBMCs from healthy persons has been described previously [17,19], whereas data concerning the release of anti-inflammatory cytokines are lacking.…”

Lack of association between chronic Chlamydophila pneumoniae infection and lung cancer among nonsmoking Chinese women in Singapore

“…9,10 Since smoking is a very strong risk factor for lung cancer, any interpretation of the C. pneumoniae-lung cancer relationship in a smoking population should consider the possibility of residual confounding effect even after adjustment using standard statistical techniques. On the other hand, in vitro studies demonstrate that infection with C. pneumoniae readily induces production of reactive oxygen species, TNF-␣, IL-1␤ and IL-8 in alveolar macrophages, 11 thus supporting its potential to act as an inflammatory stimulus and promote lung carcinogenesis. It is possible that chronic C. pneumoniae infection may act synergistically with carcinogens present in cigarette smoke to initiate or promote carcinogenesis, such that the effect is only evident in smokers.…”

Chitin Particles Are Multifaceted Immune Adjuvants

“…These studies demonstrated that immune-stimulating adjuvants like aluminum hydroxide (alum) are frequently required to elicit appropriate in vivo adaptive immunity. They also demonstrated that many of these adjuvants mediate their effects via activating innate immunity Toll-like receptors (TLRs) and NODs and inducing the production of proinflammatory cytokines (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). This can readily be appreciated in studies highlighting the important role(s) that TLRs plays in the pathogenesis of asthma-like Th2 adaptive immune responses (18) and studies that demonstrate that TLR-2 ligands such as Pam-3-cys are potent Th2 adjuvants in vivo (19,20).…”