title: Cigarette smoke exposure impairs pulmonary bacterial clearance and alveolar macrophage complement-mediated phagocytosis of Streptococcus pneumoniae.
abstract: Cigarette smoke exposure increases the risk of pulmonary and invasive infections caused by Streptococcus pneumoniae, the most commonly isolated organism from patients with community-acquired pneumonia. Despite this association, the mechanisms by which cigarette smoke exposure diminishes host defense against S. pneumoniae infections are poorly understood. In this study, we compared the responses of BALB/c mice following an intratracheal challenge with S. pneumoniae after 5 weeks of exposure to room air or cigarette smoke in a whole-body exposure chamber in vivo and the effects of cigarette smoke on alveolar macrophage phagocytosis of S. pneumoniae in vitro. Bacterial burdens in cigarette smoke-exposed mice were increased at 24 and 48 h postinfection, and this was accompanied by a more pronounced clinical appearance of illness, hypothermia, and increased lung homogenate cytokines interleukin-1beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha). We also found greater numbers of neutrophils in bronchoalveolar lavage fluid recovered from cigarette smoke-exposed mice following a challenge with heat-killed S. pneumoniae. Interestingly, overnight culture of alveolar macrophages with 1% cigarette smoke extract, a level that did not affect alveolar macrophage viability, reduced complement-mediated phagocytosis of S. pneumoniae, while the ingestion of unopsonized bacteria or IgG-coated microspheres was not affected. This murine model provides robust additional support to the hypothesis that cigarette smoke exposure increases the risk of pneumococcal pneumonia and defines a novel cellular mechanism to help explain this immunosuppressive effect.
authors.affiliation: Program in Toxicology, Department of Environmental Health Sciences, University of Michigan Health System, Ann Arbor, Michigan 48109-2029, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Phipps
authors.forename: David M
authors.initials: DM
authors.lastname: Aronoff
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Curtis
authors.forename: Deepti
authors.initials: D
authors.lastname: Goel
authors.forename: Edmund
authors.initials: E
authors.lastname: O'Brien
authors.forename: Peter
authors.initials: P
authors.lastname: Mancuso
mesh_terms: D000818:Animals; D015169:Colony Count, Microbial; D003165:Complement System Proteins / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D016207:Cytokines; D012906:Smoke; D003165:Complement System Proteins