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Reduced memory CD4+ T-cell generation in the circulation of young children may contribute to the otitis-prone
Sharad K Sharma1, Janet R Casey, Michael E Pichichero
1Center for Infectious Disease and Vaccine Immunology, Research Institute, Rochester General Hospital, Rochester, New York 14621, USA.
Insights
Children prone to recurrent ear infections (acute otitis media) show poor T-helper memory responses and reduced antibody production against common bacteria like Streptococcus pneumoniae and Haemophilus influenzae.
Area of Science:
- Immunology
- Pediatrics
- Infectious Diseases
Background:
- Recurrent acute otitis media (AOM) in children is linked to immunologic dysfunction.
- Poor antibody response is associated with the otitis-prone condition, but the mechanism is unclear.
Purpose of the Study:
- To investigate the mechanistic explanation for immunologic dysfunction in otitis-prone children.
- To compare T-helper memory responses in otitis-prone versus non-otitis-prone children.
Main Methods:
- Peripheral blood mononuclear cells from children with AOM or nasopharyngeal colonization were stimulated with bacterial antigens.
- Pathogen-specific CD4(+) T-helper memory responses were analyzed using multi-parameter flow cytometry.
Main Results:
- Otitis-prone children had significantly reduced functional CD4(+) T cells producing key cytokines (IFN-γ, IL-2, IL-4, IL-17a).
- Reduced Immunoglobulin (Ig) G responses suggest compromised B-cell function due to poor T-cell help.
- Cytokine production patterns were similar when stimulated with Staphylococcal enterotoxin B.
Conclusions:
- Otitis-prone children exhibit suboptimal T-helper memory and reduced IgG responses to Streptococcus pneumoniae and Haemophilus influenzae.
- This immune dysfunction contributes to their susceptibility to recurrent AOM infections.
Background:
An explanation for the immunologic dysfunction that causes children to be prone to repeated episodes of acute otitis media (AOM) has long been sought. Poor antibody response has been associated with the otitis-prone condition; however, there is no precise mechanistic explanation for this condition.
Methods:
Non-otitis-prone and otitis-prone children with AOM or nasopharyngeal (NP) colonization caused by either Streptococcus pneumoniae or Haemophilus influenzae were compared for pathogen-specific CD4(+) T-helper memory responses by stimulating peripheral blood mononuclear cells using 6 vaccine candidate S. pneumoniae and 3 H. influenzae protein antigens. Samples were analyzed by multi-parameter flow cytometry.
Results:
Significantly reduced percentages of functional CD45RA(Low) memory CD4(+) T cells producing specific cytokines (interferon γ, interleukin [IL]-2, IL-4 and IL-17a) were observed in otitis-prone children following AOM and NP colonization with either S. pneumoniae or H. influenzae. Immunoglobulin (Ig) G responses to the studied protein antigens were reduced, which suggests that antigen-specific B-cell function may be compromised as a result of poor T-cell help. Staphylococcal enterotoxin B stimulated similar cytokine patterns in memory CD4(+)T cells in both groups of children.
Conclusions:
Otitis-prone children have suboptimal circulating functional T-helper memory and reduced IgG responses to S. pneumoniae or H. influenzae after colonization and after AOM; this immune dysfunction causes susceptibility to recurrent AOM infections.
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