1. The olfactory system is a direct portal for bacterial pathogens to the brain.
The olfactory system is a direct portal for bacterial pathogens to the brain. (A) The cilia of olfactory sensory neurons penetrate the nasal mucosa and provide a direct pathway from the external environment to the CNS. Olfactory sensory neurons in the olfactory epithelium are supported by sustentacular cells and replaced by proliferation and differentiation of basal stem cells, and their axons pass through the lamina propria and cribriform plate of the skull to synapse with mitral cells in the glomeruli of the olfactory bulb. Microbial pathogens can potentially access the brain through the olfactory epithelium via axonal transport, by travel within olfactory ensheathing cells that surround the axons, or external to these cells, within the perineural space and by passage through holes in the cribriform plate to access the subarachnoid space. (Also see references 101 and 428.) (B and C) Coronal section through the olfactory system of an OMP-ZsGreen × S100β-DsRed transgenic reporter mouse (429, 430). (B) Primary olfactory neurons (green) reside in the olfactory epithelium, which lines the nasal cavity (NC). S, septum. The neurons project axons to the olfactory bulb (OB) within the CNS. The boxed region is shown in panel C. (C) Bundles of olfactory axons project from the olfactory epithelium (OE) through the cribriform plate (CP; chondrocytes are bright red) and enter the nerve fiber layer (NFL), which forms the outer layer of the olfactory bulb. Olfactory ensheathing cells (dull red, arrows) surround the axon bundles. (D) Sagittal section through the olfactory bulb and nasal cavity of a mouse that was intranasally inoculated with B. pseudomallei (green), with invasion of the nerve fiber layer of the olfactory bulb in the region indicated by the arrow. (E) A higher-power view of the ventral nerve fiber layer shows bacterial infestation within the nasal cavity (NC) and the olfactory epithelium (OE) and invasion of the NFL by bacteria. (Inset) Higher-power view of B. pseudomallei (green) within the nerve fiber layer. The scale bar found in panel B is equivalent to 500 μm (B), 65 μm (C), 750 μm (D), 300 μm (E), and 70 μm (inset).
Samantha J. Dando et al. Clin. Microbiol. Rev. 2014; doi: /CMR