Streptococcus pneumoniaeburden and nasopharyngeal inflammation during acute otitis media

Abstract

Streptococcus pneumoniae (Spn) is a common respiratory pathogen and a frequent cause of acute otitis media (AOM) in children. The first step in bacterial pathogenesis of AOM is the establishment of asymptomatic colonization in the nasopharynx. We studied Spn bacterial burden in conjunction with neutrophil recruitment and inflammatory gene transcription and cytokine secretion in samples of nasal wash collected from normal and otitis-prone children during health, viral upper respiratory infection without middle ear involvement (URI) and AOM. We found no significant associations between otitis-prone status and any of the measured parameters. However, Spn bacterial burden was significantly correlated with neutrophil recruitment, transcription of IL-8, TNF-α and SOD2, and secretion of TNF-α. We also found that transcription of IL-8 and TNF-α mRNA by neutrophils was significantly correlated with the secretion of these cytokines into the nasopharynx. We conclude that Spn bacterial burden in the NP is a major determinant of neutrophil recruitment to the NP and activity during URI and AOM, and that neutrophils are contributors to the secretion of IL-8 and TNF-α in the NP when the Spn burden is high.

Dynamic changes in innate immune and T cell function and composition at the nasal mucosa across the human lifespan

“…In contrast to our findings, in one previous study in which nasal aspirates were collected in children with acute otitis media, upper respiratory infections or without infection, recruitment of neutrophils to the nasopharynx correlated with Spn density (37). However, the previous study used qPCR for the genes CD16 , CD18 and CD62L on nasal aspirate pellets to quantify neutrophils, which might not as accurately measure neutrophil counts as flow cytometry, since qPCR reflects both the cellular composition and gene expression levels of individual cells.…”

Three Innate Cytokine Biomarkers Predict Presence of Acute Otitis Media and Relevant Otopathogens

“…We found that measurement of elevated serum S100A12 when children in our study were healthy identified those who were AOM prone with an AUC of 0.9. This is consistent with a recent investigation by our group, which found that variations in nasopharyngeal innate immune gene transcription, cytokine secretion, and neutrophil recruitment during AOM and URI were largely attributable to variations in S. pneumoniae bacterial burden, rather than otitis proneness [25]. The levels of the measured cytokines in nasal washes are low due to dilution in the nasal wash.…”

Factors influencing PCV13 specific antibody response in Danish children starting in day care

“…IL8 and IL1B play a crucial role in protection against both hepatitis B and S. pneumoniae, and our findings of an increase in PCV13 antibody response in children vaccinated against hepatitis B might be due to of an increased activation of the mucosal immune system. Our findings of an increased expression of IL8 and IL1B in pneumococcal carriers is supported by others [30][31][32] . Neutrophils are known to be critical in the protection against and the clearance of S. pneumoniae 33,34 and are recruited to the site of colonization through IL8.…”

“…Other studies have found a higher expression of IL8 and IL1B in serum in hepatitis B virus (HBV) infected patients [26][27][28] , while another study found mainly IL-10 to be expressed in HBV infected patients and HBV-vaccinated individuals 29 . Mucosal expression of IL8 and/or IL1B indicates activation of the mucosal immune system, which is expected in the presence of bacteria 30 . We measured the expression of the cytokines in buccal swabs, while the carriage of pneumococci was determined from nose swabs.…”