Diminished ICAM-1 expression and impaired pulmonary clearance of nontypeable Haemophilus influenzae in a mouse model of chronic obstructive pulmonary disease/emphysema.
The airways of patients with chronic obstructive pulmonary disease (COPD) are continually colonized with bacterial opportunists like nontypeable Haemophilus influenzae (NTHi), and a wealth of evidence indicates that changes in bacterial populations within the lung can influence the severity of COPD. In this study, we used a murine model for COPD/emphysema to test the hypothesis that COPD affects pulmonary clearance. Mice were treated with a pulmonary bolus of elastase, and as reported previously, the lungs of these mice were pathologically similar to those with COPD/emphysema at approximately 1 month posttreatment. Pulmonary clearance of NTHi was significantly impaired in elastase-treated versus mock-treated mice. While histopathologic analysis revealed minimal differences in localized lung inflammation between the two groups, lower levels of intercellular adhesion molecule 1 (ICAM-1) were observed for the airway epithelial surface of elastase-treated mice than for those of control mice. Following infection, elastase-treated mice had lung pathology consistent with pneumonia for as long as 72 h postinfection, whereas at the same time point, mock-treated mice had cleared NTHi and showed little apparent pathology. Large aggregates of bacteria were observed within damaged lung tissue of the elastase-treated mice, whereas sparse individual bacteria were observed in lungs of mock-treated mice at the same time point postinfection. Additional infection studies showed that NTHi mutants with biofilm defects were less persistent in the elastase-treated mice than the parent strain. These findings establish a model for COPD-related infections and support the hypotheses that ICAM-1 promotes clearance of NTHi. Furthermore, the data indicate that NTHi may form biofilms within the context of COPD-related infections.
Pang
Bing
B
Departments of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
Hong
Wenzhou
W
West-Barnette
Shayla L
SL
Kock
Nancy D
ND
Swords
W Edward
WE
D000818:Animals; D018441:Biofilms; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000209:etiology*; D006193:Haemophilus influenzae / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D051379:Mice; D009079:Mucociliary Clearance / Q000502:physiology*; D011656:Pulmonary Emphysema / Q000150:complications* / Q000382:microbiology* / Q000503:physiopathology*
D018799:Intercellular Adhesion Molecule-1
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