# Interactions of Cryptococcus neoformans with mononuclear phagocytes in the brain

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $231,190

## Abstract

Project Summary
 Cryptococcus neoformans is a pathogenic fungus, accounting for 181,000 deaths each year, worldwide.
After inhalation of C. neoformans, the fungus grows in the lung; if the fungal growth is not controlled in the lung,
the fungus can migrate to the central nervous system, causing fatal meningoencephalitis, particularly in immune
compromised individuals including HIV/AIDS patients. Cryptococcal meningoencephalitis is a leading cause of
HIV/AIDS patients. To cause meningoencephalitis, C. neoformans must invade the brain across the blood-brain
barrier and replicate in the brain parenchyma. However, after entering the brain, these invading fungal cells will
encounter brain resident macrophages as well as recruited inflammatory monocytes and their derivatives. The
outcome of the interactions between C. neoformans and these mononuclear phagocytes will determine the
progression of the disease. Thus, the mechanism behind the interactions of C. neoformans with these
mononuclear phagocytes is fundamental for understanding cryptococcal pathogenesis. So far, little is known
about the interactions between C. neoformans and mononuclear phagocytes in the brain parenchyma after its
crossing the blood-brain barrier. Based on our compelling preliminary data, we hypothesize that C. neoformans
evolved strategies to escape from host defense and that mononuclear phagocytes orchestrate fungal
pathogenesis as well as clearance. By employing genetically engineered C. neoformans strains and their
reconstitute strains as well as genetically engineered animals, we will characterize the complex interactions of
invading C. neoformans with mononuclear phagocytes and determine how the fungus escapes from host
defense in the brain in vivo. If successful, these studies would reveal novel insights into mechanisms of fungal
pathogenesis and host-pathogen interactions, providing scientific basis for targeting mononuclear phagocytes
aimed at inhibiting fungal growth in the brain.

## Key facts

- **NIH application ID:** 10766275
- **Project number:** 5R21AI173611-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Meiqing Shi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $231,190
- **Award type:** 5
- **Project period:** 2023-01-19 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10766275

## Citation

> US National Institutes of Health, RePORTER application 10766275, Interactions of Cryptococcus neoformans with mononuclear phagocytes in the brain (5R21AI173611-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10766275. Licensed CC0.

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