# T cell/astrocyte fusions as a novel form of trained immunity to infection

> **NIH NIH R21** · DUKE UNIVERSITY · 2024 · $196,912

## Abstract

Abstract:
Could fusion between two disparate cell types generate an unconventional memory of infection? Would this
hybrid cell protect against tomorrow’s pandemics or promote neurodegeneration and cognitive decline? In virally
infected mice, we serendipitously discovered the presence of long-lived cellular fusions between astrocytes, a
major glial cell type in the central nervous system (CNS), and antiviral CD8+ T lymphocytes (T cells), which
infiltrate the CNS following an upper airway infection. Remarkably, these T cell/astrocyte hybrids retain the
cellular structure of an astrocyte but maintain gene expression only present in the T cell genome. While tissue-
resident memory T cells are known to remain in the CNS after infection, T cell/astrocyte fusions represent an
entirely novel cell fate that we consistently observe. This suggests that the transfer of genetic material from T
cells could represent a widespread phenomenon associated with astrocyte reactivity. Histological studies of
human brains have described hematopoietic fusions within the CNS, particularly in inflammatory settings, but
the driving forces, mechanisms, and implications are unknown. Human pathogens, including those that cause
upper respiratory infections (URI), directly infect or impact the CNS with symptoms ranging from mild
inflammation to overt encephalitis and have been associated with cognitive changes and neurodegeneration,
including “brain fog” associated with Influenza and Covid-19. These varying impacts on brain function are likely
multifactorial but regional alterations in CNS gene expression are readily observed in animal models. We
hypothesize that T cell/astrocyte hybrids represent a novel cell type possessing an engrained memory of
inflammation that contributes to inflammatory and neurodegenerative processes. We will establish parameters
that govern astrocyte and T cell hybrid formation and identify a core signature and biological consequences of
infection-driven cell hybridization on inflammatory and immune processes.

## Key facts

- **NIH application ID:** 10861079
- **Project number:** 5R21NS133561-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** E. Ashley Moseman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $196,912
- **Award type:** 5
- **Project period:** 2023-06-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861079

## Citation

> US National Institutes of Health, RePORTER application 10861079, T cell/astrocyte fusions as a novel form of trained immunity to infection (5R21NS133561-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10861079. Licensed CC0.

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