Cryptococcus neoformans
is an encapsulated, hetero-basidiomycetous fungus producing infections in
severely immunosuppressed host like inHIV infection, organ transplantation,
hematologicalmalignancy or patients receiving high doses of corticosteroids(1-3).
It is acquired through
inhalation of basidiospore or yeast cells and remains localized in lungs but
due to its neurotropic nature, disseminates to the central nervous system (CNS)
by escaping from lungs in individuals with depressed CMI.Lung being the port of
entry of Cryptococcus; local
pulmonary defensemechanism is believed to play an important role in the control
of infection, whereas, extrapulmonary dissemination causing meningoencephalitis
and meningitis are the most common clinical manifestations of cryptococcosis
progression causing mortality in immunosuppressed individuals (4).

Immune responses in the CNS are limited by the
presence of unique effector cells, such as microglia, astrocytes and the blood
brain barrier (BBB). BBB is a layer of tightly packed capillary endothelial
cells which restricts the normal migration of cells and soluble factors to the
brain and protects the brain from chemical and infectious damage (5-6). Several
in vivo studies have depicted that
the fungus crosses the blood-brain barrier (BBB) either (i) directly
interacting with brain endothelial cells, leading to endocytosis and subsequent
transcytosis of free fungi; (ii) disruption of BBB endothelial cell junctions,
allowing paracellular passage of free fungi and (iii) as a passenger inside
host phagocytes either transcellularly or paracellularly using “Trojan Horse”
mechanism (7). However, the detail mechanism of entry of this route is yet to
be clarified. Microglia, the resident immune cells and the obligatory antigen
presenting cells of the central nervous system (CNS), plays an important role
in maintaining the CNS homeostasis. Within the CNS, these resident phagocytes
become activated upon interaction with the pathogen and up-regulate the
expression of activation markers like CD11b, CD25, MHC II (8-9) and CD45 (10) as
well as other stimulatory molecules.  The
inflammatory response is mediated by the activated microglia, respond to the
neuronal damages and remove them by phagocytic mechanism. So, activation of brain
microglia is a hallmark of brain pathology.