Figure 1.

Various proposed routes for listerial entry into the brain. (a) Entry via the blood-brain barrier (BBB). The BBB is comprised of the microvascular endothelial cells connected by tight junctions and supported by astrocytes and pericytes. Passage through the microvascular endothelium proceeds in a transcellular manner, with the bacteria either inducing endocytosis into the cells by interacting with the receptors on the cellular surface or being carried across it in infected monocytes. 1—brain tissue; 2—microvascular capillary lumen; 3—microvascular endothelium; 4—astrocyte; 5—pericyte; 6—macrophage. (b) Entry via the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB is comprised of the choroid plexus epithelial cells connected by tight junctions—the endothelium of the choroid plexus is fenestrated and presents no obstacles to the bacteria. Passage through the choroid plexus epithelium is transcellular, either direct—by induction of endocytosis into the cells—or indirect—within infected monocytes, similar to passage through the BBB. 1—cerebrospinal fluid (CSF); 2—choroid plexus capillary lumen; 3—choroid plexus endothelium; 4—choroid plexus epithelium; 5—connective tissue; 6—macrophage. (c) Entry via the trigeminal nerve. Damage to the stratified squamous epithelium that forms the top layer of oral mucosa opens a path for bacteria from contaminated food to enter the submucosa, where they can be phagocytized by either resident macrophages or recruited phagocytes. Lm is able to survive within these cells and to spread further to the nerve endings of the trigeminal nerve, along which it can travel to the brain stem. 1—trigeminal nerve ending; 2—oral cavity; 3—stratified squamous epithelium of the oral mucosa; 4—submucosa; 5—Lm-contaminated food; 6—wound in the oral mucosa; 7—resident macrophage; 8—recruited phagocyte. (d) Entry via the olfactory epithelium. The ciliated endings of olfactory sensory neurons are located at the surface of olfactory epithelium, supported by epithelial cells and covered in mucus. The axons of olfactory sensory neurons form bundles that pass through the ethmoid bone of the skull and end in the olfactory bulb. Lm can access these neurons when liquids contaminated with Lm (such as vaginal secretions ingested during childbirth) are ingested into the nasal cavity, and traveling along them provides a direct route to the brain. 1—olfactory bulb; 2—nasal cavity; 3—ethmoid bone; 4—supporting epithelium; 5—olfactory neuron; 6—olfactory nerve fiber.