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Infection and Immunity, November 2008, p. 4959-4967, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00664-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Diminished ICAM-1 Expression and Impaired Pulmonary Clearance of Nontypeable Haemophilus influenzae in a Mouse Model of Chronic Obstructive Pulmonary Disease/Emphysema{triangledown}

Bing Pang,1 Wenzhou Hong,1,{dagger} Shayla L. West-Barnette,1,{ddagger} Nancy D. Kock,2 and W. Edward Swords1*

Departments of Microbiology and Immunology,1 Pathology and Comparative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina2

Received 28 May 2008/ Returned for modification 2 July 2008/ Accepted 3 September 2008

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 ~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.

* Corresponding author. Mailing address: 5101A Gray Building, Medical Center Boulevard, Winston-Salem, NC 27157. Phone: (336) 713-5049. Fax: (336) 716-9928. E-mail: wswords{at}wfubmc.edu

{triangledown} Published ahead of print on 15 September 2008.

Editor: J. N. Weiser

{dagger} Present address: Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI.

{ddagger} Present address: NIDCD/NIH, Bethesda, MD.

Infection and Immunity, November 2008, p. 4959-4967, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00664-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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