The role of the macrophage in lung disease mediated by bacteria.
Respiratory infections are a major cause of human morbidity and a leading cause of death. The lower respiratory tract is a sterile environment and host defense is well developed to clear bacteria. This response includes both humeral factors and resident and recruited cells. The alveolar macrophage is an integral component and its long-lifespan aids function. Following low-dose challenge alveolar macrophages clear bacteria from the lung, employing an over-lapping set of microbicidal strategies. At a higher-dose the phagocytic capacity of alveolar macrophages is overwhelmed but alveolar macrophages help orchestrate the inflammatory response. In the resolution phase of infection alveolar macrophages contribute to apoptosis induction and clearance of recruited cells. This process down-regulates pro-inflammatory cytokine production. Macrophage function is controlled by induction of apoptosis. Delayed-onset macrophage apoptosis contributes both to bacterial clearance and to resolution of the inflammatory response. Mcl-1, an anti-apoptotic protein with a very short half-life, is a key regulator of macrophage survival and therefore of host responses to common bacterial pathogens in the lung. Studies involving Streptococcus pneumoniae and other respiratory bacteria are discussed to illustrate these points and ephasise that the timing of macrophage apoptosis is important in determining its overall effect on the host pathogen interaction.
Marriott
Helen M
HM
Section of Infection, Inflammation and Immunity, University of Sheffield School of Medicine and Biomedical Sciences, Sheffield, UK.
Dockrell
David H
DH
D017209:Apoptosis / Q000502:physiology; D001424:Bacterial Infections / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000502:physiology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000502:physiology; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology
D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2