Evidence of functional cell-mediated immune responses to nontypeable Haemophilus influenzae in otitis-prone children

Abstract

Otitis media (OM) remains a common paediatric disease, despite advances in vaccinology. Susceptibility to recurrent acute OM (rAOM) has been postulated to involve defective cell-mediated immune responses to common otopathogenic bacteria. We compared the composition of peripheral blood mononuclear cells (PBMC) from 20 children with a history of rAOM (otitis-prone) and 20 healthy non-otitis-prone controls, and assessed innate and cell-mediated immune responses to the major otopathogen nontypeable Haemophilus influenzae (NTHi). NTHi was a potent stimulator of inflammatory cytokine secretion from PBMC within 4 hours, with no difference in cytokine levels produced between PBMC from cases or controls. In the absence of antigen stimulation, otitis-prone children had more circulating Natural Killer (NK) cells (p<0.01), particularly NKdim (CD56lo) cells (p<0.01), but fewer CD4+ T cells (p<0.01) than healthy controls. NTHi challenge significantly increased the proportion of activated (CD107a+) NK cells in otitis-prone and non-otitis-prone children (p<0.01), suggesting that NK cells from otitis-prone children are functional and respond to NTHi. CD8+ T cells and NK cells from both cases and controls produced IFNγ in response to polyclonal stimulus (Staphylococcal enterotoxin B; SEB), with more IFNγ+ CD8+ T cells present in cases than controls (p<0.05) but similar proportions of IFNγ+ NK cells. Otitis-prone children had more circulating IFNγ-producing NK cells (p<0.05) and more IFNγ-producing CD4+ (p<0.01) or CD8+ T-cells (p<0.05) than healthy controls. In response to SEB, more CD107a-expressing CD8+ T cells were present in cases than controls (p<0.01). Despite differences in PBMC composition, PBMC from otitis-prone children mounted innate and T cell-mediated responses to NTHi challenge that were comparable to healthy children. These data provide evidence that otitis-prone children do not have impaired functional cell mediated immunity.

Panel 8: Vaccines and immunology

“…Together these data suggest that PCV10-induced PD antibodies may indeed be able to impact on OM development, but also that population and age-related differences are important to assess when evaluating potential vaccine effects. Seppanen et al compared the differences of innate and cell-mediated immune responses between otitis-prone and NOP children, and found that innate and T cell-mediated responses to NTHi infection were similar despite differences in PBMC composition [99].…”

Cellular Immune Response against Nontypeable Haemophilus influenzae Infecting the Preinflamed Middle Ear of the Junbo Mouse

“…Dendritic cells isolated from OM-prone children show lower major histocompatibility complex class II (MHC-II) expression on their surfaces (4), indicating that they are less able to induce a T-cell maturation response. Also, natural killer cells increase in the blood of children with chronic suppurative OM (CSOM), suggesting a possible role of these cells in middle ear infection (12, 13). In the rat model of AOM, induced by severing the soft palate, local proliferation of macrophages, dendritic cells, natural killer (NK) cells, and T and B lymphocytes was observed on day 5 postinoculation (14), suggesting an involvement of the local lymphatic system in the middle ear cellular and inflammatory response.…”

Mutation in Fbxo11 Leads to Altered Immune Cell Content in Jeff Mouse Model of Otitis Media

“…Analysis carried out on otitisprone children has shown similar findings; children prone to OM have a higher proportion of NK cells in blood compared to a healthy control group. The authors of the study postulate that the increase in NK cell numbers is due to prolonged exposure to upper respiratory tract infection (Seppanen et al, 2018). However, our current study provides the possibility of a genetic link being responsible for the increase in the circulating NK cells.…”