Elucidation of Cryptococcus neoformans-elicited immuno-modulation within the host

An under studied opportunistic fungal pathogen, Cryptococcus constitutes a genus within the Basidiomycota class of the fungal kingdom. Inhalation of the infectious propagules of Cryptococcus neoformans leads to its deposition in the pulmonary alveoli. In the immunocompetent individuals, the infection is progressively cleared. In immuno-compromised patients, reactivation of infection is often fatal with patients gradually developing pneumonia and meningoencephalitis, even in the presence of an aggressive antifungal drug therapy. With the expansion of immunocompromised population, cryptococcal meningitis have become a global health concern in the modern world. It remains one of the most frequent cause of death, after TB, amongst AIDS patients worldwide. Recent estimates suggest that about 223,000 new cases of cryptococcal meningitis are diagnosed every year, that causes over 181,000 deaths. Therefore, it is essential to focus our attention on understanding its pathogenesis.

We aim to elucidate:

• the process of C. neoformans-mediated deregulation of lipid homeostasis and implication of epigenetic modifications in this immunomodulation.

• the global transcriptome profile upon C. neoformans infection in murine macrophages to obtain a holistic understanding of the host-pathogen interaction.

• the mechanism of C. neoformans mediated epigenetic modulation and identify the genes and pathways hijacked by the pathogen to facilitate its own replication and survival within the host.

Investigations into discrete host signalling pathways deflected upon infection would enable us to devise host-directed strategies for therapeutic interventions against cryptococcal infections. With an escalation in the incidences of HIV infection as well as immune deficiency disorders, investigating the pathogenesis of such opportunistic pathogens becomes even more important. The dissection of distinct epigenetic mechanisms hijacked by C. neoformans to secure itself a beneficial niche inside the macrophages might potentially provide an opportunity to target disease progression at an early stage itself.