# Macrophage activation connects impairment of Histoplasma proliferation with phagosomal copper restriction

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2020 · $195,000

## Abstract

PROJECT SUMMARY
Control of primary fungal pathogens such as Histoplasma capsulatum requires the adaptive immune response
to activate macrophages. Without macrophage activation, Histoplasma yeasts invade and thrive within these
host cells. Following activation, macrophages become restrictive to fungal growth, however the mechanisms
underlying this change are only partially known. Preliminary work shows that transition to this restrictive state
correlates with a switch from phagosomes containing high concentrations of copper to a copper-limited state,
which imposes nutritional limitations to fungal growth. This proposal will develop and optimize the necessary
methodology to isolate Histoplasma-containing compartments from the macrophage to facilitate biochemical
studies of this important macrophage organelle. This will enable determination of the trace element and
protein composition of the Histoplasma-containing phagosome. Phagosomal copper dynamics and the
cytokine signals that regulate phagosome copper levels will be confirmed in vivo using fluorescent
Histoplasma yeasts as a live probe of phagosomal copper availability. Comparative protein analyses between
phagosomes from Histoplasma-permissive macrophages and from Histoplasma-restrictive macrophages will
be performed to identify candidate host factors that mediate the activation-dependent limitation of phagosome
copper necessary for control of intracellular pathogen replication.

## Key facts

- **NIH application ID:** 9872110
- **Project number:** 5R21AI137714-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Chad A Rappleye
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,000
- **Award type:** 5
- **Project period:** 2019-02-13 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872110

## Citation

> US National Institutes of Health, RePORTER application 9872110, Macrophage activation connects impairment of Histoplasma proliferation with phagosomal copper restriction (5R21AI137714-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872110. Licensed CC0.

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