Influenza Virus Infection Decreases Tracheal Mucociliary Velocity and Clearance ofStreptococcus pneumoniae

Abstract

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.

Continuous mucociliary transport by primary human airway epithelial cells in vitro

“…Mucociliary dysfunction is also a major component of other diseases, including chronic obstructive pulmonary disease (COPD) (34) and asthma (9). Furthermore, disruption of normal MCC in healthy individuals, e.g., by viral infection, can result in subsequent bacterial pneumonias (33). Thus there is a profound need for both a better understanding of the development and regulation of normal MCC and the development of therapeutic approaches to improve ciliary clearance in individuals with the disease.…”

Dinámica y patología del barrido mucociliar como mecanismo defensivo del pulmón y alternativas farmacológicas de tratamiento

“…Infecciones pueden inducir hiperplasia y metaplasia de células caliciformes e hipertrofia de glándulas submucosas con producción copiosa de mucinas, alterando la composición del moco y el balance entre secreción y remoción de la vía aérea, generando tapones mucosos que obstruyen el paso del aire, con consecuencias clínicas como hipoxemia, hipercapnia y prolongación de la infección 48,62 . Patógenos, como Mycoplasma pneumoniae pueden secretar factores de virulencia capaces de cambiar la orientación de los cilios o disminuir su frecuencia de batido 10,58,59 . Infecciones virales pueden aumentar la expresión de ecto-ATPasas que agotan el ATP extracelular, inhibiendo la secreción de Cl -y aumentando la viscosidad del moco 3 .…”

Viral infection of the lung: Host response and sequelae

“…142 IAV replication in the respiratory epithelium leads to impairment of mucosalciliary clearance and increased bacterial colonization. 143,144 Secondary infections primarily coincide with resolution of inflammation and the onset of reparative responses rather than early viral replication, 142,145,146 indicating host responses also have a significant effect on the susceptibility to bacterial superinfection. In experimental models the release of type I interferons and IFN-during viral clearance from the lung negatively affects the ability of lung-infiltrating neutrophils and macrophages, respectively, to control bacterial infection.…”