Bacterial infection of the brain: how bacteria penetrate the CNS by invading peripheral nerves

Bacterial infections of the central nervous system (CNS), though uncommon, are associated with very high rates of morbidity and mortality. Recent research has also highlighted the correlation between pathogens and chronic diseases of the CNS, such as neurodegenerative disorders, particularly Alzheimer’s disease. Whilst some bacteria can cross the blood-brain/blood-cerebrospinal fluid barriers, to date, other pathways by which bacteria enter the CNS remain largely unknown. Identifying alternative paths by which pathogens can enter the CNS is thus important for developing novel strategies preventing CNS infection and potential long-term sequelae. Novel evidence suggests some bacterial species (as well as certain viruses and amoebae) can enter the brain via the cranial nerves innervating the nasal cavity, particularly the olfactory nerve that mediates the sense of smell and connects the nasal cavity with the olfactory bulb in the forebrain. The trigeminal nerve also innervates the nasal cavity and constitutes another invasion path. Only a handful of pathogens are thought to use cranial nerves to reach the brain; certain Chlamydia species (spp.) being amongst these. Chlamydia pneumoniae is to date the bacterium with the strongest established link to Alzheimer’s disease. Previous research by our laboratory has also demonstrated that the bacterium causing the tropical disease melioidosis, Burkholderia pseudomallei, can invade both the olfactory and trigeminal nerves, travel along these nerves, to then infect the CNS (the olfactory bulb and brainstem, respectively). We have also previously shown that in outbred mice, the olfactory nerve is resistant to B. pseudomallei infection. The nasal mucosa contains both innate and adaptive immune components and prevents many infections. If pathogens penetrate the mucosal barrier and reach nerves, glial cells of the nerves can also combat the infection. Whilst only a few macrophages are present inside the olfactory nerve fascicles, olfactory nerve glial cells, termed olfactory ...