# Interaction of Human Pulmonary Macrophage and Dendritic Cell Subsets with Cryptococcus neoformans

> **NIH NIH P20** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $203,702

## Abstract

Cryptococcus neoformans meningitis occurs in approximately 225,000 individuals with AIDS each year, resulting
in over 181,000 annual deaths. C. neoformans is an opportunisitic fungal pathogen that is inhaled and
subsequently escapes the lungs and disseminates to the central nervous system where life-threatening
meningitis occurs. Host factors that determine whether C. neoformans initially survives or is destroyed by
pulmonary phagocytes remain poorly defined, presenting a major gap in understanding how this pathogen
ultimately causes meningitis and death. It is postulated that C. neoformans uses macrophages for transport from
the lung to the brain to cause meningitis. However, C. neoformans can be killed in some macrophages but
replicates in others. In addition, we and others have shown that dendritic cells (DCs), a critical innate phagocyte
in the lung, can engulf and destroy C. neoformans, but like macrophages this may be restricted to a subset of
DCs. Our preliminary data indicate subsets of primary human pulmonary macrophages and DCs interact with C.
neoformans and exhibit differential anti-cyptococcal activities. Some innate phagocyte subsets kill C.
neoformans, and others do not. Therefore, we hypothesize that subsets of innate phagocytes in the lung
are capable of restricting C. neoformans growth through direct intracellular fungicidal activity absent in
permissive subsets of DCs and macrophages. We will monitor and characterize the fungicidal response of
human pulmonary phagocyte subsets to C. neoformans and then examine roles of mediators of fungicidal activity
(iNOS, ROS, and lysosomal enzyme cathepsin B) in each subset (Aim 1). Next, we will identify differentially
regulated genes and signaling pathways that may coordinate fungicidal activity in each subset following
interaction with C. neoformans (Aim 2). Consequently, our studies will identify phagocyte subsets responsible
for anti-cryptocccal activity or permissive fungal growth and identify the host genes and signaling pathways that
may be responsible for regulating these responses.

## Key facts

- **NIH application ID:** 9853464
- **Project number:** 1P20GM134973-01
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Karen Lynn Wozniak
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $203,702
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853464

## Citation

> US National Institutes of Health, RePORTER application 9853464, Interaction of Human Pulmonary Macrophage and Dendritic Cell Subsets with Cryptococcus neoformans (1P20GM134973-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9853464. Licensed CC0.

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