Cigarette Smoke Exposure Increases Myeloid Cell Production and Lung Bacterial Clearance in Mice

Basilico, Paola; Cremona, Tiziana Patrizia; Oevermann, Anna; Piersigilli, Alessandra; Benarafa, Charaf (2015). Cigarette Smoke Exposure Increases Myeloid Cell Production and Lung Bacterial Clearance in Mice. American journal of respiratory cell and molecular biology, 54(3), pp. 424-435. American Lung Association 10.1165/rcmb.2015-0017OC

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Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most COPD patients are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or following smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared to air-exposed mice when infected 16-24 hours post-exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to comparable levels as those of control mice suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production prior to infection in mice exposed to cigarette smoke relative to mice never exposed or following smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1β and GM-CSF in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using serpinb1a-deficient mice with reduced neutrophil numbers and treatment with G-CSF showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Basilico, Paola; Cremona, Tiziana Patrizia; Oevermann, Anna; Piersigilli, Alessandra and Benarafa, Charaf

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1044-1549

Publisher:

American Lung Association

Language:

English

Submitter:

Barbara Gautschi-Steffen

Date Deposited:

18 Feb 2016 10:47

Last Modified:

26 Jun 2016 02:11

Publisher DOI:

10.1165/rcmb.2015-0017OC

PubMed ID:

26273827

Uncontrolled Keywords:

Otitis Pneumococcus Pneumonia Secondhand smoke Serpin

URI:

https://boris.unibe.ch/id/eprint/75650

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