# Molecular mechanisms of a multi-tissue innate immune response

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $347,225

## Abstract

PROJECT SUMMARY/ABSTRACT
Innate immunity plays important roles as first line defense and primer for adaptive immunity to protect against
infection, and its excessive prolonged activation promotes chronic inflammatory diseases. While the main
molecular players and signaling pathways involved in innate immunity have been identified, more research is
needed to understand how signaling among multiple tissues triggers innate immune responses at the
organismal level. Since studying multi-tissue innate immune responses remains challenging in vertebrate
systems, we address this question in a simple invertebrate model. Drosophila melanogaster has been key in
the discovery of innate immunity, and it is likewise expected to be an excellent model to understand molecular
mechanisms that drive more complex, multi-tissue innate immune responses. Specifically, we propose to
investigate a new model of an innate immune response in adult Drosophila, which involves the combination of
a reservoir of immune cells (hemocytes), respiratory epithelium, and domains of the anatomically colocalizing
immune tissue of the fat body. In this model, we focus on the expression of Drosocin as a readout, which
promotes survival after bacterial infection. We find that hemocytes, and specifically their signaling by the NFkB-
related Imd pathway, are required for the induction of Drosocin expression in the respiratory epithelium and
locally restricted domains of the fat body. However, while Imd signaling in hemocytes is required, it is not
sufficient to trigger the Drosocin response.
We hypothesize that immune cells act as sentinels of bacterial infection that relay a (so far unidentified) signal
to the respiratory epithelium and fat body, which in response upregulate Drosocin. Drosocin has, at
endogenous expression levels, anti-bacterial function and promotes animal survival after bacterial infection.
We propose to (1) identify hemocyte signal/s that trigger the Drosocin response in other tissues, and (2)
identify the signaling pathways within tissues that relay the Drosocin response.
This work is significant because insights from this Drosophila model are expected to increase our
understanding of the molecular mechanisms that drive multi-tissue innate immune responses in a variety of
organisms across phyla, thereby extending the concept of `inter-organ/-tissue communication' to innate
immunity. New mechanistic principles identified in this model are expected to inform vertebrate research and
inspire therapeutic approaches that curb or enhance multi-tissue innate immune responses, which could be
tailored toward a variety of medical needs and conditions.

## Key facts

- **NIH application ID:** 10178043
- **Project number:** 5R01GM131094-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** DANA LEANNE JONES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $347,225
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178043

## Citation

> US National Institutes of Health, RePORTER application 10178043, Molecular mechanisms of a multi-tissue innate immune response (5R01GM131094-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10178043. Licensed CC0.

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