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    Area of Science:

    • Mycology
    • Immunology
    • Neuroscience

    Background:

    • Cryptococcus neoformans causes fungal meningitis in HIV/AIDS patients.
    • Mechanisms of cryptococcal meningoencephalitis are not fully understood.
    • Inositol transporters (ITR) are previously shown to be essential for Cryptococcus virulence.

    Purpose of the Study:

    • Investigate the host immune response to a C. neoformans itr1aΔ itr3cΔ double mutant.
    • Understand the role of inositol transporters in cryptococcal brain infections.
    • Elucidate the impact of reduced capsule production on host immunity.

    Main Methods:

    • Murine model of intra-cerebral infection.
    • Genome-wide transcriptome shotgun sequencing (RNA-Seq).
    • Quantitative real-time PCR (qRT-PCR).

    Main Results:

    • The itr1aΔ itr3cΔ mutant showed attenuated virulence in the murine brain infection model.
    • Mutant infection led to significant activation of host protective immunity pathways (TNF-α, IFN-γ).
    • Reduced glucuronoxylomannan (GXM) secretion was observed in the mutant, indicating ITRs' role in capsule production.

    Conclusions:

    • Reduced GXM production in the mutant may contribute to increased immune activation.
    • Inositol utilization pathways are critical for Cryptococcus capsule production.
    • Targeting ITRs could modulate host immune responses against cryptococcal meningitis.