Characterisation of the immune response in otitis media

Abstract

Acute otitis media is the most common illness diagnosed during early childhood that can cause significant morbidity (Brook,1994) and sometimes can cause irreversible sequelae such as a hearing defect and subsequent learning difficulties (Klein,1994). The aims of the research presented here were to study some aspects of the middle ear defence mechanisms in both immune and non-immune rats following experimental otitis media (OM) with two pathogens nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (M. catarrhalis). This study also aimed at developing a suitable technique for preparing immunohistochemical staining of middle ear sections (chapter 2). A previous study has shown that a regime where rats received an IPP immunisation combined with an IT boost was effective in enhancing clearance of a middle ear infection with the same strain of NTHi and also in the presence of a concomitant viral infection (Moore et al,2001). Results of this study have shown that for NTHi infection a distinct cellular influx to the middle ear in the immune rats was accompanied by an enhanced bacterial clearance compared to the non-immunised rats (chapter 3). This cellular influx was responsible for the remarkable reduction in the bacterial number. The sharp decline in PMNs numbers in the NTHi immunised rats that followed complete bacterial clearance at 72h post infection (Table 3.1) indicate a more effectively controlled down regulation of this cell infiltrate than the non-immunised rats. For M. catarrhalis infection, there was no difference in cell infiltrate between immune and non-immune rats, but enhanced clearance of the bacteria were observed for the immune animals. The histopathological changes in the middle ear mucosa of rats with experimentally induced infection were studied to provide a better understanding about the distribution of the inflammatory cells and changes in the mucosa during the first 24h post challenge with NTHi and M. catarrhalis (Chapter 4). These changes have not been previously studied for the two pathogens at 24h post challenge in rats. Induced infections with the two pathogens were found to produce similar histopathological changes but more inflammatory infiltration was observed within the infected mucosa with NTHi than that seen with M. catarrhalis. The infections were characterized by increased thickness of the middle ear mucosa, Eustachian tube mucosa, periosteum and tympanic membrane. There was also an increase in the number and size of small blood vessels at all sites, and these small blood vessels seem to be the source of the inflammatory infiltration into the middle ear mucosa and middle ear cavity during the infection. These findings provided an essential background to the immunohistochemical study. The effect of mucosal immunisation on the distribution of CD4+T cells and CD8+T cells has not been investigated previously. Results of the present study (Chapter 5) show the pattern of distribution of these cells during the first 48h post infection with NTHi in the rat. The number of CD4+and CD8+T cells peaked at 24h post infection in the nonimmunised animal and were highest at 48h post-infection in the immunised rats. The difference in response in the immunised rats may represent regulation of the inflammatory response by the immune system. The inflammatory response regulation is indicated by the difference in cellular influx into the immune rats and the response in the immune rats that corresponds to enhanced bacterial clearance prior to a decrease in numbers of inflammatory cells once the bacteria was no longer detected (Chapter 3). This resolution of the inflammatory mass would reduce the opportunity for continued damage to local tissue. These changes are also supported by the reduction in the thickness of the middle ear mucosa of the immunised rats especially at 24h and 48h post-infection (Chapter 5). This study has shown that there are distinct differences in the rate of bacterial clearance and cellular changes in the middle ear mucosa and tympanic bulla in immunised rats during a middle ear infection. Future studies are still required to gain a better understanding of differences in the inflammatory response for both pathogens, NTHi and M. catarrhalis.

Date of Award	2002
Original language	English
Supervisor	Janelle Kidd (Supervisor), Ruth Foxwell (Supervisor) & A Cripps (Supervisor)