Cellular Immune Response in Young Children Accounts for Recurrent Acute Otitis Media

ABSTRACT Nontypeable Haemophilus influenzae (NTHi) is a major pathogen causing acute otitis media (AOM). The pathology of AOM increases during long-term infection in the middle ear (ME), but the host cellular immune response to bacterial infection in this inflamed environment is poorly understood. Using the Junbo mouse, a characterized NTHi infection model, we analyzed the cellular response to NTHi infection in the Junbo mouse middle ear fluid (MEF). NTHi infection increased the total cell number and significantly decreased the proportion of live cells in the MEF at day 1, and this further decreased gradually on each day up to day 7. Flow cytometry analysis showed that neutrophils were the dominant immune cell population in the MEF and that NTHi infection significantly increased their proportion whereas it decreased the monocyte, macrophage, and dendritic cell proportions. Neutrophil and macrophage numbers increased in blood and spleen after NTHi infection. The T-cell population was dominated by T-helper (Th) cells in noninoculated MEF, and the effector Th (CD44+) cell population increased at day 2 of NTHi infection with an increase in IL-12p40 levels. Sustained NTHi infection up to 3 days increased the transforming growth factor β levels, decreasing the effector cell population and increasing the T-regulatory (T-reg) cell population. In the preinflamed ME environment of the Junbo mouse, neutrophils are the first responder to NTHi infection followed by T-reg immune suppressive cells. These data indicate that sustained NTHi infection in the ME induces the immune suppressive response by inducing the T-reg cell population and reducing immune cell infiltration, thus promoting longer-term infection.

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Comparative Analysis of the Humoral Immune Response to Moraxella catarrhalis and Streptococcus pneumoniae Surface Antigens in Children Suffering from Recurrent Acute Otitis Media and Chronic Otitis Media with Effusion

Clinical and Vaccine Immunology ◽

10.1128/cvi.05630-11 ◽

2012 ◽

Vol 19 (6) ◽

pp. 914-918 ◽

Cited By ~ 9

Author(s):

Suzanne J. C. Verhaegh ◽

Kim Stol ◽

Corné P. de Vogel ◽

Kristian Riesbeck ◽

Eric R. Lafontaine ◽

...

Keyword(s):

Immune Response ◽

Otitis Media ◽

Humoral Immune Response ◽

Moraxella Catarrhalis ◽

Otitis Media With Effusion ◽

Acute Otitis Media ◽

Chronic Otitis Media ◽

Content Type ◽

Humoral Immune ◽

Recurrent Acute Otitis Media

ABSTRACTA prospective clinical cohort study was established to investigate the humoral immune response in middle ear fluids (MEF) and serum against bacterial surface proteins in children suffering from recurrent acute otitis media (rAOM) and chronic otitis media with effusion (COME), using Luminex xMAP technology. The association between the humoral immune response and the presence ofMoraxella catarrhalisandStreptococcus pneumoniaein the nasopharynx and middle ear was also studied. The levels of antigen-specific IgG, IgA, and IgM showed extensive interindividual variation. No significant differences in anti-M. catarrhalisand anti-S. pneumoniaeserum and MEF median fluorescence intensity (MFI) values (anti-M. catarrhalisand antipneumococcal IgG levels) were observed between the rAOM or COME groups for all antigens tested. No significant differences were observed forM. catarrhalisandS. pneumoniaecolonization and serum IgG levels against theMoraxellaand pneumococcal antigens. Similar to the antibody response in serum, no significant differences in IgG, IgA, and IgM levels in MEF were observed for allM. catarrhalisandS. pneumoniaeantigens between OMM. catarrhalis-orS. pneumoniae-positive and OMM. catarrhalis-orS. pneumonia-negative children suffering from either rAOM or COME. Finally, results indicated a strong correlation between antigen-specific serum and MEF IgG levels. We observed no significantin vivoexpressed anti-M. catarrhalisor anti-S. pneumoniaehumoral immune responses using a range of putative vaccine candidate proteins. Other factors, such as Eustachian tube dysfunction, viral load, and genetic and environmental factors, may play a more important role in the pathogenesis of OM and in particular in the development of rAOM or COME.

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Tympanostomy in young children with recurrent otitis media. A long-term follow-up study

The Journal of Laryngology & Otology ◽

10.1017/s0022215100143592 ◽

1999 ◽

Vol 113 (3) ◽

pp. 207-211 ◽

Cited By ~ 13

Author(s):

Hannu Valtonen ◽

Yrjö Qvarnberg ◽

Juhani Nuutinen

Keyword(s):

Young Children ◽

Otitis Media ◽

Otitis Media With Effusion ◽

Acute Otitis Media ◽

Safe Procedure ◽

Tube Extrusion ◽

Final Study ◽

Recurrent Acute Otitis Media ◽

Long Term Follow Up ◽

Ventilation Tubes

AbstractA total of 305 children, five to 16 months of age, were treated from 1983–1984 with ventilation tubes – Shah vent Teflon tube – inserted under local anaesthesia for recurrent acute otitis media (RAOM) or otitis media with effusion (OME). The final study group comprised 281 children (92.1 per cent) monitored prospectively for five years, 185 in the OME-group and 96 in the RAOM-group. For the first insertion of tubes the average ventilation period was 15.4 months. Re-tympanostomy, with adenoidectomy simultaneously at the first time was performed in 99 ears (35.2 per cent); once in 27.0 per cent, twice in five per cent, and three times in 3.2 per cent. Mastoidectomy due to otorrhoea was performed in three ears (1.1 per cent). The children in the OME-group were at higher risk of repeated post-tympanostomy otorrhoea episodes than children in the RAOM-group. These episodes of otorrhoea during the first insertion of ventilation tubes significantly increased both the tube extrusion rate and the need for subsequent re-tympanostomies. No major complications were caused by the tympanostomy procedure as such. It is concluded that early tympanostomy is a safe procedure in young children with RAOM or OME. However, parents should be carefully informed of risks of post-tympanostomy otorrhoea and recurrent disease after insertion of ventilation tubes necessitating subsequent tube insertion, especially in children with OME.

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Gestational pertussis vaccination and the infant’s cellular immune response against whole-cell pertussis vaccine in the first year of life

10.1101/697722 ◽

2019 ◽

Author(s):

Carolina Argondizo-Correia ◽

Lourdes Rehder de Andrade Vaz-de-Lima ◽

Elaine Uchima Uehara ◽

Eder Gatti Fernandes ◽

Helena Keico Sato ◽

...

Keyword(s):

Immune Response ◽

Young Children ◽

Cellular Immune Response ◽

Early Life ◽

Cellular Response ◽

Booster Dose ◽

Maternal Antibodies ◽

Maternal Vaccination ◽

Maternal Immunisation ◽

Cellular Immune

AbstractPertussis resurgence worldwide calls for new prevention strategies, as the recently incorporated vaccine booster dose during pregnancy, whose aim is to protect newborns from infection. In Brazil, maternal Tdap vaccination is recommended since 2014, and we reported that this strategy promotes high transplacental transfer of anti-PT IgG and it is effective in protecting infants early in life. Young children are the most susceptible group and with higher mortality rates, however, it is not well known whether the elicited anti-pertussis maternal antibodies could influence in the children’s immune responses further in life, especially after their own vaccination against pertussis. Considering this scenario, we conducted a study with children born to mothers who either received or not the booster dose during pregnancy, after their primary pertussis vaccination, in order to investigate the first impact of maternal immunisation on the response to infant immunisation regarding the cellular immune response, while comparing with data from the literature. As transfer of maternal antibodies could result in attenuation of the immune response to vaccination in infants, this study performed to determine whether higher levels of maternal antibodies could influence in the immune response of infants to the whole-pertussis vaccination series. Results showed no difference in cytokine production between groups, a first suggestion that maternal vaccination may not interfere with recognition and cellular response generation to vaccination. This data, together with humoral immunity and epidemiological studies, is important for the implementation of maternal immunisation strategies nationwide and will contribute to assure public policies regarding vaccination schemes.ImportancePertussis, or whopping cough, is a respiratory infectious disease caused by a bacterial agent, resulting in violent coughs and possibly death in vulnerable groups, such as young children and neonates. It is known that pregnant mothers transfer antibodies to their developing foetuses for protection in early life, however anti-pertussis antibodies are not highly detected in young children. Thus, a pertussis maternal vaccination was implemented to increase maternal anti-pertussis antibodies levels in pregnant women and therefore the transference to the foetus. However, maternal antibodies can also interfere in the child immune response in the first months of life. The significance of our research is in analysing the cellular immune response of children born from pertussis-vaccinated mothers, which will give a first glimpse on how maternal antibodies could modulate the child’s response to pertussis in early life.

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