# Cryptococcal Exploitation of the Blood-Brain Barrier

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $204,688

## Abstract

Abstract
Cryptococcus neoformans (C. neoformans) is an important cause of life-threatening opportunistic central
nervous system (CNS) infection in HIV-1-infected patients. For areas of the world where HIV-1 is endemic, C.
neoformans is the most common cause of culture-positive meningitis. Several lines of evidence from human
cases and experimental animal models of C. neoformans CNS infection indicate that cerebral capillaries are
the portal of C. neoformans entry into the brain. Since the entry of C. neoformans into the brain occurred in the
cerebral microvasculature, we used the in vitro blood-brain barrier model with human brain microvascular
endothelial cells (HBMEC) to investigate cryptococcal penetration of the blood-brain barrier. We showed that
C. neoformans exhibited the ability to traverse the HBMEC monolayer in vitro and penetrate into the brain in
vivo in the mouse model of experimental hematogenous C. neoformans CNS infection. The underlying
mechanisms involved with C. neoformans penetration of the blood-brain barrier, however, remain incompletely
understood. Our preliminary screen of HBMEC infected with C. neoformans for determination of host factors
revealed globular C1q receptor (gC1qR). The role of gC1qR in C. neoformans penetration of the blood-brain
barrier has not been previously recognized, and it remains unclear how gC1qR contributes to cryptococcus
penetration of the blood-brain barrier. gC1qR is a multifunctional protein and shown to be expressed on the cell
surface. We hypothesize that C. neoformans exploits gC1qR for penetration of the blood-brain barrier, the
essential step in the development of cryptococcal CNS infection. This hypothesis is supported by our
demonstration that HBMEC with gC1qR knockdown exhibited significantly less C. neoformans penetration.
gC1qR does not have a consensus sequence of transmembrane domain, and the goal of this application is to
elucidate how gC1qR contributes to C. neoformans penetration of the blood-brain barrier. The innovative
aspect of this R21 exploratory application is to investigate a new target (gC1qR) exploited by C. neoformans
for penetration of the blood-brain barrier. The information derived from this application will provide a new
paradigm for investigating the pathogenesis of C. neoformans CNS infection.

## Key facts

- **NIH application ID:** 10128375
- **Project number:** 5R21AI147699-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Brendan Cormack
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $204,688
- **Award type:** 5
- **Project period:** 2020-03-17 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128375

## Citation

> US National Institutes of Health, RePORTER application 10128375, Cryptococcal Exploitation of the Blood-Brain Barrier (5R21AI147699-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10128375. Licensed CC0.

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