Chapter 34 : Invasion of into the Central Nervous System

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This chapter reviews the current state of knowledge regarding how invades into the central nervous system (CNS). An understanding of the unique characteristics of the blood-brain barrier (BBB) is essential to comprehend the potential mechanisms by which blood-borne microbes, including , transverse it. Brain microvascular endothelial cells (BMECs), which line the capillaries supplying blood to the brain, have unique tight junctions that contribute to the barrier function of the BBB. A major function of the BBB is maintenance of the neural microenvironment by regulating the passage of molecules into and out of the brain. The role of monocytes in CNS invasion by relies first on clinical observations. When occlusion occurs in blood vessels supplying the CNS, invasion into damaged tissue can occur. Additionally, at early time points, invasion of the CNS by did not occur from the surface of the brain via the invasion of the blood vessels supplying the leptomeninges (pia mater and arachnoid). The other cryptococcal virulence factor that has been linked to brain invasion is urease, which is produced by nearly all clinical isolates of . Urease expression contributes to the CNS invasion by enhancing yeast sequestration within cerebral microcapillary beds during hematogenous spread. Meningoencephalitis is the most common and serious clinical manifestation of cryptococcosis. Remarkable progress has been made toward elucidating the means by which gains access into the CNS.

Citation: Dromer F, Levitz S. 2011. Invasion of into the Central Nervous System, p 465-471. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch34

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White Blood Cells
Fungal Infections
Cryptococcus gattii
Major Histocompatibility Complex
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Image of FIGURE 1

Typical aspect of a dilated VirchowRobin space during cryptococcal meningoencephalitis. Semithin section of the brain cortex of a mouse with severe meningoencephalitis after inoculation with showing the pseudocysts centered by a brain capillary and filled with numerous capsulated yeasts either free or inside phagocytes.

Citation: Dromer F, Levitz S. 2011. Invasion of into the Central Nervous System, p 465-471. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch34
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Image of FIGURE 2

Semithin section of leptomeninges from a mouse with severe meningoencephalitis after inoculation with . (a) Dilatation of a Virchow-Robin space is visible with the meningeal capillary containing numerous red blood cells. (b) A mononuclear cell probably carrying a yeast cell can be seen inside the capillary. (c) On the left, a small capillary with a yeast inside the cytoplasm of an endothelial cell. Cryptococci are also seen in the leptomeningeal space outside the capillaries, either (d) as poorly encapsulated yeasts inside vacuolated macrophagelike cells apparently touching the outside membrane of the vessel or (e) as free and with thick capsules.

Citation: Dromer F, Levitz S. 2011. Invasion of into the Central Nervous System, p 465-471. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch34
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