Figure 1.

(a) Fungi enter the brain through either direct inoculation, or by crossing the blood–brain barrier (BBB). Direct inoculation can be the result of a traumatic event, or iatrogenically through neurosurgery. Fungi can cross the BBB by being taken up by endothelial cells (transcellular), degrading the tight junctions between the cells (paracellular), or carried across the BBB in a phagocyte (‘Trojan horse’). Brain Image adapted from https://www.health.harvard.edu/heart-health/the-crucial-controversial-carotid-artery-part-i-the-artery-in-health-and-disease. (b) Fungi are detected in the brain by resident glial cells (microglia, astrocytes) through Toll-like receptors (TLR) and C-type lectin receptors (CLR). Glial cells can then directly engage the fungi, clearing them from the brain, or recruit immune cells through the release of cytokines and chemoattractants. Innate immune cells such as neutrophils, and adaptive immune cells such as T_H1 and T_H17 lymphocytes are effective at clearing the infection. However, excessive inflammation and immunotoxicity can lead to irreversible neurological damage.