Intramacrophage ROS Primes the Innate Immune System via JAK/STAT and Toll Activation

Sveta Chakrabarti,Sandhya S Visweswariah

doi:10.1016/j.celrep.2020.108368

Sveta Chakrabarti, Sandhya S Visweswariah

Open Access

https://doi.org/10.1016/j.celrep.2020.108368

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Journal: Cell Reports	Publication Date: Nov 1, 2020
Citations: 76	License type: cc-by

Affiliation: Indian Institute of Science Bangalore

Abstract

SummaryTissue injury is one of the most severe environmental perturbations for a living organism. When damage occurs in adult Drosophila, there is a local response of the injured tissue and a coordinated action across different tissues to help the organism overcome the deleterious effect of an injury. We show a change in the transcriptome of hemocytes at the site of tissue injury, with pronounced activation of the Toll signaling pathway. We find that induction of the cytokine upd-3 and Toll receptor activation occur in response to injury alone, in the absence of a pathogen. Intracellular accumulation of hydrogen peroxide in hemocytes is essential for upd-3 induction and is facilitated by the diffusion of hydrogen peroxide through a channel protein Prip. Importantly, hemocyte activation and production of reactive oxygen species (ROS) at the site of a sterile injury provide protection to flies on subsequent infection, demonstrating training of the innate immune system.

Highlights

The adult Drosophila is an excellent model to study host responses to infection and injury (Lemaitre and Hoffmann, 2007)
We identify an aquaporin-like channel protein, Prip, that is required for the diffusion of H2O2 into hemocytes
Transcriptome of Adult Hemocytes to Wounding To gain further insights into the mechanisms underlying hemocyte activation upon clean injury, we conducted genome-wide mRNA sequencing of hemocytes harvested from unchallenged adult flies and 1 h post-injury

Summary

Introduction

The adult Drosophila is an excellent model to study host responses to infection and injury (Lemaitre and Hoffmann, 2007). The cellular immune arm in Drosophila comprises cells called hemocytes. They circulate freely in the body cavity of Drosophila, function as professional phagocytes of the immune system, and can be considered the fly equivalent of bonemarrow-derived macrophages. Molecular details of how hemocytes contribute to host development reveal their role in clearing apoptotic corpses and patterning tissues in Drosophila (Wood and Martin, 2017). Once development is complete, very little is known about whether hemocytes play roles that contribute to the overall health of the host. A few studies have shown that Drosophila hemocytes maintain host health through their ability to carry out long-range communication to other tissues during a systemic wound response (Lee and Miura, 2014). Hemocytes serve as messengers between the wound site and distant tissues such as the fat body and intestinal tract (Agaisse et al, 2003; Chakrabarti et al, 2016)

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