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Review
. 2017 Feb 24;3(1):10.
doi: 10.3390/jof3010010.

The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System

Lilit Aslanyan  1 , David A Sanchez  2 , Silvana Valdebenito  3 , Eliseo A Eugenin  4 , Raddy L Ramos  5 , Luis R Martinez  6
Affiliations
Review

The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System

Lilit Aslanyan et al. J Fungi (Basel). .

Abstract

Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing life threatening meningoencephalitis in patients with impaired immunity. This microbe primarily infects the host via inhalation but has the ability to disseminate to the central nervous system (CNS) either as a single cell or inside of macrophages. Upon traversing the blood brain barrier, C. neoformans has the capacity to form biofilm-like structures known as cryptococcomas. Hence, we will discuss the C. neoformans elements contributing to biofilm formation including the fungus' ability to survive in the acidic environment of a macrophage phagosome and inside of the CNS. The purpose of this mini-review is to instill fresh interest in understanding the importance of biofilms on fungal pathogenesis.

Keywords: CNS; Cryptococcus neoformans; biofilms; cryptococcomas; macrophages.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Biofilm-like cryptococcomas (brain lesions) in hippocampal tissue sections 14 days after intratracheal inoculation of C. neoformans strain H99 in a C57BL/6J mouse. (A) Confocal microscopy of the hippocampus in the brain of an infected animal with cap59 (acapsular mutant). Capsule deficient mutants are cleared by phagocytic cells in the lungs of infected animals and are unable to reach the central nervous system; (B) Immunofluorescent image of a hippocampal tissue section of a mouse infected with wild-type C. neoformans H99 displaying large cryptococcomas (yellow arrows) filled with yeasts cells and abundant amounts of capsular polysaccharide released (white arrow heads) in the area; (C,D) Cryptococcomas are characterized by significant neuronal loss due to biofilm-like colonization of brain tissue; (E,F) High magnification images show a substantial number of yeast cells attached to neuronal tissue. For panels A–F, capsular-specific monoclonal antibody 18B7 (monoclonal antibody 18B7; green) was used to label fungal cells and capsular polysaccharide released. GFAP (red) and DAPI (blue) staining were used to label the cell bodies and nuclei of astrocytes, respectively. Scale bars: A,B = 230 µm; C = 87 µm; D = 35 µm; E = 21 µm; F = 17 µm.
Figure 2
Figure 2
Cryptococoma formation in the gray and white matter of the midbrain and hindbrain 14 days after intratracheal inoculation of C. neoformans strain H99 in a C57BL/6J mouse. (A) Nissl-stained sagittal section indicating location of cyptococomas observed in the superior colliculus (SC; black arrow), inferior colliculus (IC; black asterisk), and cerebellum (Crb; red arrowhead); (B) Low- and high-magnification of a white matter cryptococoma (left and right panels) in the anterior cerebellum; (C) Low- and high-magnification of a white matter cryptococoma (left and right panels) in the inferior colliculus showing loss of parenchymal neurons and few macrophages except along the borders of the lesion (arrows); (D) Low- and high-magnification of a white matter cryptococoma (left and right panels) in the dorsal superior colliculus with marked presence of Nissl-stained microglia/macrophages. Panel A was adapted from the Allen Brain Mouse Reference Atlas (http://atlas.brain-map.org). Black arrows in right panels indicate cryptococcal cells. Scale bars: A = 1047 µm; B–D left panels = 200 μm; B–D right panels = 50 μm.
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