Increased Myeloid Cell Production and Lung Bacterial Clearance in Mice Exposed to Cigarette Smoke.
Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most patients with COPD 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 after smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared with air-exposed mice when infected 16 to 24 hours after exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to levels comparable to 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 before infection in mice exposed to cigarette smoke with mice never exposed or after smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1β and granulocyte-macrophage colony-stimulating factor 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 granulocyte colony-stimulating factor 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.
1 Theodor Kocher Institute.|2 Graduate School for Cellular and Biomedical Sciences.
Paola
P
Basilico
1 Theodor Kocher Institute.|2 Graduate School for Cellular and Biomedical Sciences.
Tiziana P
TP
Cremona
3 Neurocenter, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, and.
Anna
A
Oevermann
4 Institute of Animal Pathology, University of Bern, Bern, Switzerland; and.|5 School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Alessandra
A
Piersigilli
1 Theodor Kocher Institute.
Charaf
http://orcid.org/0000-0002-2049-7769
C
Benarafa
D000818:Animals; D058491:Bacterial Load; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007700:Kinetics; D007762:Labyrinthitis / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D022423:Myeloid Cells / Q000276:immunology* / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity
C587672:IL1B protein, mouse; C583355:IL1R1 protein, mouse; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; C522950:Serpinb1a protein, mouse; D015843:Serpins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
inflammation; innate immunity; myelopoiesis; otitis; pneumonia