Journal Article

Influenza Virus Infection Decreases Tracheal Mucociliary Velocity and Clearance of Streptococcus pneumoniae

Pittet, Lynnelle A., Rutkowski, Melanie R., Harmsen, Allen G., Hall-Stoodley, Luanne

2010

Overview

Influenza virus infections increase susceptibility to secondary bacterial infections, such as pneumococcal pneumonia, resulting in increased morbidity and mortality. Influenza-induced tissue damage is hypothesized to increase susceptibility to Streptococcus pneumoniae infection by increasing adherence to the respiratory epithelium. Using a mouse model of influenza infection followed by S. pneumoniae infection, we found that an influenza infection does not increase the number of pneumococci initially present within the trachea, but does inhibit pneumococcal clearance by 2 hours after infection. To determine whether influenza damage increases pneumococcal adherence, we developed a novel murine tracheal explant system to determine influenza-induced tissue damage and subsequent pneumococcal adherence. Murine tracheas were kept viable ex vivo as shown by microscopic examination of ciliary beating and cellular morphology using continuous media flow for up to 8 days. Tracheas were infected with influenza virus for 0.5-5 days ex vivo, and influenza-induced tissue damage and the early stages of repair to the epithelium were assessed histologically. A prior influenza infection did not increase pneumococcal adherence, even when the basement membrane was maximally denuded or during the repopulation of the basement membrane with undifferentiated epithelial cells. We measured mucociliary clearance in vivo and found it was decreased in influenza-infected mice. Together, our results indicate that exposure of the tracheal basement membrane contributes minimally to pneumococcal adherence. Instead, an influenza infection results in decreased tracheal mucociliary velocity and initial clearance of pneumococci, leading to an increased pneumococcal burden as early as 2 hours after pneumococcal infection.

• Publisher: American Thoracic Society
• Subject: Animals / Bacterial Adhesion / Basement Membrane - metabolism / Basement Membrane - microbiology / Basement Membrane - pathology / Basement Membrane - virology / Cilia - metabolism / Cilia - microbiology / Cilia - pathology / Cilia - virology / Female / Influenza A Virus, H1N1 Subtype - metabolism / Mice / Orthomyxoviridae Infections - metabolism / Orthomyxoviridae Infections - microbiology / Orthomyxoviridae Infections - pathology / Pneumococcal Infections - metabolism / Pneumococcal Infections - pathology / Pneumococcal Infections - virology / Respiratory Mucosa - metabolism / Respiratory Mucosa - microbiology / Respiratory Mucosa - pathology / Respiratory Mucosa - virology / Streptococcus pneumoniae - metabolism / Time Factors / Trachea - metabolism / Trachea - microbiology / Trachea - pathology / Trachea - virology