Danger signals activate a putative innate immune system during regeneration in a filamentous fungus.

Elizabeth Medina-Castellanos,Alfredo Herrera-Estrella,José Manuel Villalobos-Escobedo,Meritxell Riquelme,Cei Abreu-Goodger,Nick D Read,A Aziz Aboobaker

doi:10.1371/journal.pgen.1007390

Abstract

The ability to respond to injury is a biological process shared by organisms of different kingdoms that can even result in complete regeneration of a part or structure that was lost. Due to their immobility, multicellular fungi are prey to various predators and are therefore constantly exposed to mechanical damage. Nevertheless, our current knowledge of how fungi respond to injury is scarce. Here we show that activation of injury responses and hyphal regeneration in the filamentous fungus Trichoderma atroviride relies on the detection of two danger or alarm signals. As an early response to injury, we detected a transient increase in cytosolic free calcium ([Ca2+]c) that was promoted by extracellular ATP, and which is likely regulated by a mechanism of calcium-induced calcium-release. In addition, we demonstrate that the mitogen activated protein kinase Tmk1 plays a key role in hyphal regeneration. Calcium- and Tmk1-mediated signaling cascades activated major transcriptional changes early following injury, including induction of a set of regeneration associated genes related to cell signaling, stress responses, transcription regulation, ribosome biogenesis/translation, replication and DNA repair. Interestingly, we uncovered the activation of a putative fungal innate immune response, including the involvement of HET domain genes, known to participate in programmed cell death. Our work shows that fungi and animals share danger-signals, signaling cascades, and the activation of the expression of genes related to immunity after injury, which are likely the result of convergent evolution.

Highlights

The idea of regenerating lost body parts has fascinated humans since the beginning of history [1]
Danger signals activate hyphal regeneration supported by CONACYT grant - Investigacion en Fronteras de la Ciencia (FON.INST./117/2016) to AHE https://www.conacyt.gob.mx/ and the CABANA project, which is funded by the BBSRC under the The Global Challenges Research Fund (GCRF) Growing Research Capability call, contract number BB/P027849/1
We show that activation of injury responses and hyphal regeneration in a filamentous fungus relies on the detection of danger signals used by plants and animals

Summary

Introduction

The idea of regenerating lost body parts has fascinated humans since the beginning of history [1]. Human imagination was further captured upon witnessing the extraordinary capacity of species from almost all Phyla to, upon damage, regenerate a lost part or structure [1]. Multicellular organisms establish interactions with a great variety of other, potentially harmful, organisms throughout their life. They require mechanisms to detect injury and to distinguish self- from non-self. Multicellular organisms require alarm signals known as Damage-Associated Molecular Patterns (DAMPs) to contend with a wound. In this regard, normal cellular components released into extracellular spaces, such as DNA, ATP and Ca2+, represent reliable signals that indicate to other cells the disruption of tissue, and trigger a response [2]. Intracellular signaling after injury involves Mitogen Activated Protein Kinases (MAPKs), as in the case of axon regeneration after spinal cord injury in vertebrates [3] and herbivory in plants [4]

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Conclusion