# Immune modulation during infection by a secreted fungal polysaccharide

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $381,250

## Abstract

Systemic fungal infections are a major public health concern, annually causing over 1.3 million deaths
worldwide and costing healthcare systems billions of dollars. These infections are difficult and expensive to
treat due to a limited number of drugs and poor understanding of infectious mechanisms.
 Cryptococcus neoformans is the major cause of fungal meningitis, annually responsible for
approximately 1 million infections and 600,000 deaths worldwide. The majority of these cases are in HIV/AIDS
patients. Infections begin in the lungs but in severe cases spread to the brain, causing a difficult-to-treat
meningitis infection. C. neoformans produces a large cell surface capsule, the predominant component of
which is the polysaccharide glucuronoxylomannan (GXM). GXM is necessary for infection, facilitates C.
neoformans's ability to evade phagocytosis and destruction by immune cells, and inhibits immune responses.
 In addition to cell surface GXM, free secreted GXM (exo-GXM) has been long thought to play a role in
infection. Free GXM circulates in serum and cerebrospinal fluid during and after infection. However, its precise
role and biogenesis are not understood. We have identified the first mutants in this secretion pathway and will
determine how secreted GXM facilitates infection and dissemination of C. neoformans.
 We find that GXM accumulates in the tissue of infected mice before C. neoformans cells spread from
the lungs to those tissues, suggesting that exo-GXM facilitates dissemination. First, we will separate different
steps of dissemination and determine how exo-GXM contributes to each. Second, we will determine how exo-
GXM inhibits the immune response during infection by testing two hypotheses: 1) exo-GXM blocks immune cell
infiltration into tissue and 2) exo-GXM prevents maturation or differentiation of circulating leukocytes. Finally,
we will determine the molecular mechanisms of exo-GXM generation and regulation. These experiments will
separate exo-GXM function from cell surface GXM function, determine how exo-GXM modulates the
mammalian immune system during infection, and help determine whether exo-GXM could be developed as an
immunosuppressive drug.

## Key facts

- **NIH application ID:** 9962276
- **Project number:** 5R01AI130248-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** JESSICA Conrad BROWN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2018-05-24 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962276

## Citation

> US National Institutes of Health, RePORTER application 9962276, Immune modulation during infection by a secreted fungal polysaccharide (5R01AI130248-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9962276. Licensed CC0.

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