Survival curve, histochemistry, and immunohistochemistry for C57BL/6 and SCID mice infected intracranially with Cryptococcus strains. (A) Intracranial infection results in rapid death of mice infected with C. neoformans and C. gattii strain R272, which is considered hypovirulent in a pulmonary infection model. In contrast, most mice survive infection with the “hypervirulent” C. gattii VGIIa strain. (B) Histochemistry and immunohistochemistry for representative infected C57BL/6 mice. (Top panel) alcian blue counterstaining showing cryptococcal cells in the mice meninges (left-pointing arrowhead). The fungal burden is considerably lower in mice infected with C. gattii VGIIa (see also Fig. S2 in the supplemental material for a zoomed-out field of view). (Middle panel) Anti-GFAP antibody staining showing astrocytes (right-pointing arrowhead). (Bottom panel) Anti-Iba1 visualizing microglial cells (upward-pointing arrowhead). The immune response is extremely limited, particularly for C. neoformans infection, despite the significant fungal burden. There was a greater microglial response in mice infected with C. gattii VGIIb than in those infected with C. neoformans and C. gattii VGIIa. Bar, 50 μm. H&E, hematoxylin and eosin.