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Bacterial Infections

Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae

John C. Phipps, David M. Aronoff, Jeffrey L. Curtis, Deepti Goel, Edmund O'Brien, Peter Mancuso
John C. Phipps
1Program in Toxicology
2Department of Environmental Health Sciences, School of Public Health
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David M. Aronoff
3 Divisions of Infectious Diseases
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Jeffrey L. Curtis
4Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan
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Deepti Goel
2Department of Environmental Health Sciences, School of Public Health
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Edmund O'Brien
1Program in Toxicology
2Department of Environmental Health Sciences, School of Public Health
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Peter Mancuso
2Department of Environmental Health Sciences, School of Public Health
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  • For correspondence: pmancuso@umich.edu
DOI: 10.1128/IAI.00963-09
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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-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor alpha (TNF-α). 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.

  • Copyright © 2010 American Society for Microbiology
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Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae
John C. Phipps, David M. Aronoff, Jeffrey L. Curtis, Deepti Goel, Edmund O'Brien, Peter Mancuso
Infection and Immunity Feb 2010, 78 (3) 1214-1220; DOI: 10.1128/IAI.00963-09

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Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae
John C. Phipps, David M. Aronoff, Jeffrey L. Curtis, Deepti Goel, Edmund O'Brien, Peter Mancuso
Infection and Immunity Feb 2010, 78 (3) 1214-1220; DOI: 10.1128/IAI.00963-09
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KEYWORDS

Complement System Proteins
lung
Macrophages, Alveolar
phagocytosis
Smoke
Streptococcus pneumoniae

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