# Innate immunity pathways activate cell proliferation after penetrating traumatic brain injury in adult Drosophila

## TL;DR

This study shows that innate immunity pathways in fruit flies help trigger cell growth after brain injury, which may be important for recovery.

## Contribution

The study identifies a novel role for Toll and Imd pathways in cell proliferation after brain injury in Drosophila.

## Key findings

- Toll and Imd innate immunity pathways are rapidly upregulated after PTBI in Drosophila.
- Loss of Dif or Rel leads to a loss of cell proliferation following injury.
- Antimicrobial peptides are upregulated but return to baseline quickly after injury.

## Abstract

We are utilizing an adult penetrating traumatic brain injury (PTBI) model in Drosophila to investigate regenerative mechanisms after damage to the central brain. Here, we focus on cell proliferation as an early event in the regenerative process. To identify pathways that could trigger cell proliferation following PTBI, we utilized bulk RNA-Seq. We find that transcript levels for components of both Toll and Immune Deficiency (Imd) innate immunity pathways are rapidly and highly upregulated post-PTBI. We then tested mutants for the NF-κB transcription factors of the Toll and Imd pathways, Dorsal-related immunity factor (Dif) and Relish (Rel), respectively. We find that loss of either Dif or Rel results in loss of cell proliferation after injury and identify tissue-specific requirements for Dif and Rel. In addition, while the canonical downstream targets of Drosophila innate immune signalling, the antimicrobial peptides (AMPs), are upregulated following PTBI, their levels revert to near baseline within 24 hr. Taken together, these results indicate that the innate immunity pathways play an integral role in the regenerative response and that this response may not require the antimicrobial peptides. Innate immunity previously has been implicated as both a potentiator and an inhibitor of regenerative processes. Our work suggests that modulation of innate immunity may be essential to prevent adverse outcomes. Thus, this work is likely to inform future experiments to dissect regenerative mechanisms in higher organisms as well as in Drosophila.