Immunology of the Middle Ear: Role of Local and Systemic Antibodies in Clearance of Viruses and Bacteria

Abstract

Acute otitis media may be defined as the sudden onset of inflammation in the middle-ear space characterized by ear pain and a bulging, thickened, and immobile tympanic membrane. The middle-ear fluid is typically purulent. A bacterial pathogen is recovered in 75% of the episodes. Streptococcus pneumoniae predominates at 35%, followed by nontypeable Hemophilus influenzae at 25%, and Moraxella catarrhalis at 15%. The remaining 25% of middle-ear fluids are sterile and presumably represent viral infections. Increasing evidence suggests that viruses may participate in more than 50% of all acute otitis media (AOM) episodes; however, pure viral AOM is relatively uncommon. IThe natural course of AOM has not been studied in the past decade. A review of articles concerning treatment of AOM demonstrates a spontaneous self-resolution rate between 30 and 80%.24 This rate varies with the specific pathogen from a high rate of 79% with M. catarrhalis to a low rate of 11% with S. pne~moniae.'.~ The mechanisms of eradication appear to involve various host defenses, including phagocytosis and destruction within neutrophils, lysis by host products outside of the cell, immunologic destruction by antibody and complement, and drainage of pus from the middle-ear space through the eustachian tube.Ample evidence has been accumulated that supports the role of serum antibody in protecting the middle-ear space from infection. For example, the incidence of AOM is relatively low during the first six months of life when maternally acquired antibody levels are relatively high in infants. More specifically, antibody concentrations to S. pneumoniae in cord blood correlate to susceptibility to the development of pneumococcal otitis media, as does the level of antibody to nontypeable H. influenzae in older Low levels of antibody can be corrected by passive immunization with serum containing high titers of antibody. By passively raising levels of pneumococcal antibody, the frequency of otitis media is reduced. I* Active immunization with S. pneumoniae has also been associated with a reduced frequency of

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

“…Interestingly, however, a strong correlation was observed between IgG antibody levels in serum and IgG antibody levels in MEF, for both M. catarrhalis and pneumococcal proteins for the whole study cohort. This is an interesting finding, as it indicates that serum antibody levels are predictive of the presence of local (middle ear) IgG antibody (14,17) and raises the possibility that the measurement of OM pathogen-specific IgG antibodies in the middle ear may be achieved by simply measuring OM pathogen-specific IgG antibody levels in serum. At this moment in time, however, it is not known whether OM pathogen-specific IgG is actually produced locally in the middle ear or transudes into the middle ear from the general circulation (4,14).…”

Epitope Mapping of the Outer Membrane Protein P5-Homologous Fimbrin Adhesin of Nontypeable Haemophilus influenzae

“…When assayed against the four region peptides, the middle ear fluids specifically recognized and bound to the region 3 and 4 peptides, beginning approximately 4 weeks after challenge but already showing lessened reactivity 5 weeks after challenge. Since total antibody available in middle ear fluids represents both locally produced antibody as well as antibodies contributed by serum transuded into the middle ear space during inflammation (2,(16)(17)(18)(19)57), this delayed reactivity of the middle ear fluids to these peptides may have represented the prolonged period of time required for serum antibodies to transude into this highly inflamed space during an active disease of this type. However, these data may also be indicative of the time point at which region 3-and 4-specific antibodies were available for detection in this assay system despite their presence in these fluids at a much earlier point in time and for a more extended period of the disease course.…”

Antibodies Mediate Formation of Neutrophil Extracellular Traps in the Middle Ear and Facilitate Secondary Pneumococcal Otitis Media

“…We had previously demonstrated that infection with IAV induces an influx of neutrophils into the middle ear cavities of infant mice (3). Moreover, pneumococci in the ear colocalize with this influx of neutrophils (3), and neutrophils are thought to interact with antibodies in the middle ear (19). In light of the suggested role of NETs in OM (14, 15), we reasoned that antibodies in the middle ear may facilitate bacterial outgrowth by inducing NETs.…”

“…Pneumococcal OM predominately develops in the absence of preexisting immunity, with incidence peaking between 6 months (when maternal antibodies have waned) and 2 years, when specific immunity develops (19). In these immunologically naive individuals, natural antibodies may represent an important defense mechanism against influenza virus-mediated pneumococcal disease, as is seen in pneumococcal sepsis (20).…”

“…Conversely, the formation of immune complexes in the middle ear may facilitate, rather than clear, bacterial OM (21), suggesting that organ-specific differences may exist with regard to the role of antibodies during pneumococcal disease. Moreover, the ability of antibodies to interact with neutrophils in the middle ear (19), and the suggestion that neutrophils may facilitate bacterial OM (14,15), may indicate that the role of antibodies and neutrophils in pneumococcal-influenza virus OM is more complex than simply protecting against disease development.…”