Influenza A virus-induced polymorphonuclear leukocyte dysfunction in the pathogenesis of experimental pneumococcal otitis media

Abstract

The role of influenza A virus-induced polymorphonuclear leukocyte and eustachian tube dysfunction in the pathogenesis of acute purulent otitis media was studied in chinchillas. Polymorphonuclear leukocyte function, middle ear pressure, and the incidence of pneumococcal otitis media were observed after intranasal inoculation with influenza A virus, Streptococcus pneumoniae, or both. Results showed that depressed negative middle ear pressure and polymorphonuclear leukocyte chemiluminescence and chemotactic activity occurred after influenza inoculation, but not after inoculation with pneumococcus alone. The greatest incidence of pneumococcal otitis media occurred when the pneumococcus was inoculated just before the time of influenza-induced polymorphonuclear leukocyte dysfunction and negative middle ear pressure. Animals that had unilateral tympanostomy tubes placed before inoculation of influenza with pneumococcus showed no difference in the occurrence of pneumococcal otitis media in ventilated and nonventilated ears, suggesting that polymorphonuclear leukocyte dysfunction contributes more to the pathogenesis of pneumococcal otitis media than does negative middle ear pressure in this animal model.

Secondary Bacterial Infections in Influenza Virus Infection Pathogenesis

“…Middle ear inflammation, regardless of pathogenic origin, is sufficient to induce AOM. Influenza viruses can initiate this inflammation (Abramson et al 1981(Abramson et al , 1982Short et al 2013b), cause hearing loss and instigate bacterial growth within the ear cavity in a viral strain-dependent, but cell tropism independent, manner (Short et al 2013a).…”

“…Inflammation in AOM is characterized by an influx of neutrophils and expression of key proinflammatory genes (i.e., pro-IL-1b, IL-1a, and CXCL2) (Abramson et al 1981(Abramson et al , 1982Short et al 2011Short et al , 2013b. Chinchilla studies indicate that immunosuppression, rather than inflammation, is the key mechanism contributing to enhanced pneumococcal replication since influenza viruses can inhibit neutrophils and render clearance ineffective (Abramson et al 1981(Abramson et al , 1982. However, it has also been hypothesized that the enhanced bacterial growth results from nutrients becoming available in areas damaged by this response (Short et al 2013b).…”

Importance of Respiratory Viruses in Acute Otitis Media

“…Intranasal inoculation of chinchillas with influenza A virus was shown to result in negative middle-ear pressure that was not observed in animals inoculated with S. pneumoniae only (2). The extent of epithelial damage in the Eustachian tube caused by influenza A virus infection was later demonstrated in a histopathologic study in which the development of negative middle-ear pressure was associated with marked ciliary damage, disappearance of ciliated epithelial cells, and increased accumulation of mucus and cellular debris in the tubal lumen (59).…”

The Role of Influenza and Parainfluenza Infections in Nasopharyngeal Pneumococcal Acquisition Among Young Children

“…Experimental pneumococcal infection of animals previously infected with influenza results in severe disease and death [13]. Whether virulence factors common to both pathogens (ie, neuraminidase) [13] and/or other immunological host factors (eg, impairment of macrophages and neutrophil function) [17][18][19][20] mediate this interaction remains unclear. Animal studies also suggest that influenza infection facilitates the transmission of some pneumococcal serotypes [21,22].…”