Epithelial Anion Transporter Pendrin Contributes to Inflammatory Lung Pathology in Mouse Models of Bordetella pertussis Infection

• Type of Material: Article
• Authors: Karen M. Scanlon, University of Maryland; Yael Gau, University of Maryland; Jingsong Zhu, University of Maryland; Ciaran Skerry, University of Maryland; Susan Wall, Emory University; Manoocher Soleimani, University of Cincinnati; Nicholas H. Carbonetti, University of Maryland
• Language: English
• Date: 2014-10-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2014, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/IAI.02222-14
• Title of Journal or Parent Work: Infection and Immunity
• ISSN: 0019-9567
• Volume: 82
• Issue: 10
• Start Page: 4212
• End Page: 4221
• Grant/Funding Information: This work was supported by Public Health Service grant AI-101055 from the National Institute of Allergy and Infectious Diseases.
• Keywords: Infectious Diseases; Immunology; Science & Technology; EXPRESSION; TOXIN; NEUTROPHIL RECRUITMENT; WHOLE-CELL; SYNDROME GENE; BICARBONATE SECRETION; ASTHMA; RESPIRATORY-TRACT COLONIZATION; Life Sciences & Biomedicine; PROTEIN; OBSTRUCTIVE PULMONARY-DISEASE
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Pertussis disease, characterized by severe and prolonged coughing episodes, can progress to a critical stage with pulmonary inflammation and death in young infants. However, there are currently no effective treatments for pertussis. We previously studied the role of pertussis toxin (PT), an important Bordetella pertussis virulence factor, in lung transcriptional responses to B. pertussis infection in mouse models. One of the genes most highly upregulated in a PT-dependent manner encodes an epithelial transporter of bicarbonate, chloride, and thiocyanate, named pendrin, that contributes to asthma pathology. In this study, we found that pendrin expression is upregulated at both gene and protein levels in the lungs of B. pertussis-infected mice. Pendrin upregulation is associated with PT production by the bacteria and with interleukin-17A (IL-17A) production by the host. B. pertussis-infected pendrin knockout (KO) mice had higher lung bacterial loads than infected pendrin-expressing mice but had significantly reduced levels of lung inflammatory pathology. However, reduced pathology did not correlate with reduced inflammatory cytokine expression. Infected pendrin KO mice had higher levels of inflammatory cytokines and chemokines than infected pendrin-expressing mice, suggesting that these inflammatory mediators are less active in the airways in the absence of pendrin. In addition, treatment of B. pertussis-infected mice with the carbonic anhydrase inhibitor acetazolamide reduced lung inflammatory pathology without affecting pendrin synthesis or bacterial loads. Together these data suggest that PT contributes to pertussis pathology through the upregulation of pendrin, which promotes conditions favoring inflammatory pathology. Therefore, pendrin may represent a novel therapeutic target for treatment of pertussis disease.