Cryptococcus inositol utilization modulates the host protective immune response during brain infection

Tong Bao Liu, Selvakumar Subbian, Weihua Pan, Eliseo Eugenin, Jianping Xie, Chaoyang Xue

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Background: Cryptococcus neoformans is the most common cause of fungal meningitis among individuals with HIV/AIDS, which is uniformly fatal without proper treatment. The underlying mechanism of disease development in the brain that leads to cryptococcal meningoencephalitis remains incompletely understood. We have previously demonstrated that inositol transporters (ITR) are required for Cryptococcus virulence. The itr1aΔ itr3cΔ double mutant of C. neoformans was attenuated for virulence in a murine model of intra-cerebral infection; demonstrating that Itr1a and Itr3c are required for full virulence during brain infection, despite a similar growth rate between the mutant and wild type strains in the infected brain. Results: To understand the immune pathology associated with infection by the itr1aΔ itr3cΔ double mutant, we investigated the molecular correlates of host immune response during mouse brain infection. We used genome-wide transcriptome shotgun sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) methods to examine the host gene expression profile in the infected brain. Our results show that compared to the wild type, infection of mouse brains by the mutant leads to significant activation of cellular networks/pathways associated with host protective immunity. Most of the significantly differentially expressed genes (SDEG) are part of immune cell networks such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) regulon, indicating that infection by the mutant mounts a stronger host immune response compared to the wild type. Interestingly, a significant reduction in glucuronoxylomannan (GXM) secretion was observed in the itr1aΔ itr3cΔ mutant cells, indicating that inositol utilization pathways play a role in capsule production. Conclusions: Since capsule has been shown to impact the host response during Cryptococcus-host interactions, our results suggest that the reduced GXM production may contribute to the increased immune activation in the mutant-infected animals.

Original languageEnglish (US)
Article number51
JournalCell Communication and Signaling
Issue number1
StatePublished - Sep 10 2014
Externally publishedYes


  • Capsule production
  • Cellular networks
  • Cryptococcal meningoencephalitis
  • Cryptococcus neoformans
  • Genome-wide transcriptome
  • Glucuronoxylomannan
  • Host immune response
  • Immune pathways
  • Inositol transporters
  • Quantitative real-time PCR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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