Divergent mucosal and systemic responses in children in response to acute otitis media

Abstract

SummaryAcute otitis media (AOM), induced by respiratory bacteria, is a significant cause of children seeking medical attention worldwide. Some children are highly prone to AOMs, suffering three to four recurrent infections per year (prone). We previously determined that this population of children could have diminished anti-bacterial immune responses in peripheral blood that could fail to limit bacterial colonization in the nasopharynx (NP). Here, we examined local NP and middle ear (ME) responses and compared them to peripheral blood to examine whether the mucosa responses were similar to the peripheral blood responses. Moreover, we examined differences in effector cytokine responses between these two populations in the NP, ME and blood compartments at the onset of an AOM caused by either Streptococcus pneumoniae or non-typeable Haemophilus influenzae. We found that plasma effector cytokines patterned antigen-recall responses of CD4 T cells, with lower responses detected in prone children. ME cytokine levels did not mirror blood, but were more similar to the NP. Interferon (IFN)-γ and interleukin (IL)-17 in the NP were similar in prone and non-prone children, while IL-2 production was higher in prone children. The immune responses diverged in the mucosal and blood compartments at the onset of a bacterial ME infection, thus highlighting differences between local and systemic immune responses that could co-ordinate anti-bacterial immune responses in young children.

Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY

“…To determine whether there was an intrinsic T-cell defect in sOP children, we stimulated the PBMCs with Staphylococcal Enterotoxin B (SEB) and observed no difference in the percentage of memory CD45RA Low CD4 T cells producing IFN-γ, IL-4, IL-2 or IL-17a in sOP vs. NOP children (see Figure, SDC 1). 21 The results from this study showed that sOP children have suboptimal circulating functional T-helper memory cells after colonization and after AOM and this immune dysfunction contributes to susceptibility to recurrent AOM infections.…”

Early life bacterial airway colonization, local immune mediator response and risk of otitis media

“…pneumoniae colonization in children with an increasing number of episodes of AOM ( P =0.07), a finding that may be spurious, given the multiple tests performed. A previous cross-sectional study of 24 children found no difference between otitis-prone and non-prone children in the nasal expression of IL-17 during AOM [27], whereas an IL-17 receptor knockout mouse model showed higher pneumococcal load in middle ears 3 days after a nasal challenge with S. pneumoniae [28], suggesting that IL-17 expression is an important mediator in the clearance of S.…”

Management of acute otitis media in children six months of age and older

“…(5,6) A small proportion of children have lower levels of secretory immunoglobulin A or persistent biofilms in the middle ear, which may play a role in increasing the risk for recurrent AOM. (7)(8)(9) There is a clinical spectrum of middle ear infections associated with the initiation and progression of infection leading to bacterial AOM. Middle ear fluid from AOM cases often harbour both viruses and bacteria; however, children who experience spontaneous resolution of AOM are likely to have viral infections alone or to have bacterial organisms that are less virulent (eg, Moraxella catarrhalis and some strains of Haemophilus influenzae) compared with Streptococcus pneumoniae and Streptococcus pyogenes (group A streptococci [GAS]).…”