# Macrophage Reprogramming During Granuloma Formation in the Zebrafish

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $427,101

## Abstract

Abstract
Granulomas form as a conserved host response to a variety of inflammatory and infectious stimuli. As
granulomas assemble, macrophages interdigitate and undergo a striking morphological transition, taking on an
epithelioid appearance. The basis for this transformation and the consequences for disease are not fully
understood. We have identified a conserved reprogramming of macrophages that underlies the assembly and
stability of mycobacterial granulomas. Using a zebrafish model, we find that epithelial modules and structures
are induced during granuloma formation and are critical for granuloma integrity. In this project we will 1) use
long-term intravital imaging to assess key epithelial modules engaged by macrophages during granuloma
formation and how disruption of the mycobacterial granuloma can lead to improved host outcome; 2) test the
role of the IL-4/IL-13/Stat6 axis during macrophage reprogramming events; 3) based on RNA-seq analysis of
macrophages isolated from infected animals, assess the role of the sonic hedgehog (Shh) pathway in
granuloma formation, maintenance, and infection trajectory. Findings from this project will be translated into
human disease. Overall, this proposal will test the hypothesis that, in a striking parallel to mesenchymal-to-
epithelial transitions in cancer, macrophages draw on classical developmental signaling pathways to undergo
an epithelial-like transition and construct the central structure of tuberculosis. A new perspective on this critical
structure may have important implications for our understanding of disease progression and the design of new
therapeutic approaches.

## Key facts

- **NIH application ID:** 9876981
- **Project number:** 5R01AI130236-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** David M. Tobin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,101
- **Award type:** 5
- **Project period:** 2017-03-03 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876981

## Citation

> US National Institutes of Health, RePORTER application 9876981, Macrophage Reprogramming During Granuloma Formation in the Zebrafish (5R01AI130236-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9876981. Licensed CC0.

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