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Lower nasopharyngeal epithelial cell repair and diminished innate inflammation responses contribute to the onset of acute otitis media in otitis-prone children

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Abstract

About 30 % of young children experience excessive, frequent episodes of middle ear infection and are classified as acute otitis media prone (OP). Streptococcus pneumoniae (Spn) is a predominant otopathogen in OP and non-OP (NOP) children. The pathogenesis of middle ear infection involves otopathogen nasopharyngeal (NP) colonization followed by an upper respiratory viral infection that modifies the NP environment to allow a sufficient inoculum of bacteria to reflux via the Eustachian tube into the middle ear space. Here, we analyzed the NP mucosal repair response between age-matched stringently defined OP (sOP) and NOP children who progressed to middle ear infection caused by Spn. We found lower epidermal growth factor, epidermal growth factor receptor, and angiogenin cytokine concentrations in nasal washes of sOP compared with NOP children. Despite higher expression of TLR2/4 transcript expression in nasal epithelium and in polymorphonuclear cells present in nasal secretions in sOP children, sOP children had lower expression of proinflammatory cytokines such as IL-6 and IL-8 in the NP. Chemotaxis-associated cytokine expression at onset of AOM in sOP children was also lower compared with NOP children, possibly indicating a lower capacity to signal the innate immune system. We conclude that lower epithelial cell repair responses during viral infection in the NP combined with diminished innate inflammatory responses potentiate Spn pathogenesis in the sOP child.

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Acknowledgments

This work was supported by R01DC008671 awarded to Michael Pichichero. DV had support from K22AI089975. We thank Karin Pryharski for her technical help and Qingfu Xu for viral detection of patient data.

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  1. Rochester General Hospital Research Institute, Rochester General Hospital, 1425 Portland Ave., Rochester, NY, 14621, USA

    David Verhoeven, Monica Nesselbush & Michael E. Pichichero

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  1. David Verhoeven
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  2. Monica Nesselbush
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  3. Michael E. Pichichero
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Correspondence to Michael E. Pichichero.

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Verhoeven, D., Nesselbush, M. & Pichichero, M.E. Lower nasopharyngeal epithelial cell repair and diminished innate inflammation responses contribute to the onset of acute otitis media in otitis-prone children. Med Microbiol Immunol 202, 295–302 (2013). https://doi.org/10.1007/s00430-013-0293-2

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