Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

Abstract

The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor. Epistasis experiments indicate a requirement for Spätzle ligand downstream of hydrogen peroxide and protease function, both of which are known activators of wound-induced transcription. The localized activation of Toll a few cell diameters from wound edges is reminiscent of local activation of Toll in early embryonic ventral hypoderm, consistent with the hypothesis that the dorsal–ventral patterning function of Toll arose from the evolutionary cooption of a morphogen-responsive function in wound repair. Furthermore, the combinatorial activity of Toll and other signaling pathways in activating epidermal barrier repair genes can help explain why developmental activation of the Toll, ERK, or JNK pathways alone fail to activate wound repair loci.

Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants

“…These studies show the mechanisms by which Drosophila can recognise tumour cells in the body, which is an important subject. The innate immune system might recognise more common disorders, such as the loss of tissue integrity as seen in the case of breaks in the epidermal barrier or stress-related signal(s) induced by cell damage (Capilla et al, 2017). If this is the case, we might be able to clarify why the two independent innate immune pathways that are intrinsically triggered by different types of microorganisms were simultaneously activated in the mxc mbn1 mutant larvae.…”

Wound healing, calcium signaling, and other novel pathways are associated with the formation of butterfly eyespots

“…The Toll pathway is known for its ancestral role in activating the innate immune response [ 55 ], as well as a derived role in patterning the dorsal ventral axis of insect embryos [ 56 ]. Recently, the Toll pathway has also been implicated in wound epidermal closure in Drosophila [ 57 ]. Both in flies and in worms the immune system is activated by wounding to promote cell survival [ 40 , 43 , 55 ], and signals other than the presence of microbes, such as sterile wounding, can also activate the innate immune response of insects in the absence of an infection.…”

“…Interestingly, Toll is also expressed in the ectodermal cells that form the leading edge of dorsal closure in Drosophila embryos and at intersegmental boundaries [ 60 ]. Most recently, the over-expression of constitutively activated Toll was sufficient to induce wound repair genes in the undamaged epidermis of Drosophila [ 57 ], suggesting that Toll regulates a modular network that may have been co-opted to aid in eyespot origins [ 61 ]. Both Toll and its ligand, Spätzle, should be investigated in future regarding their possible role in eyespot development.…”

A Toll pathway effector protectsDrosophilaspecifically from distinct toxins secreted by a fungus or a bacterium

“…It also encompasses a second dimension, known as resilience or tolerance, which regroups the physiological mechanisms that allow the host to endure or repair damages inflicted by the virulence factors of pathogens or by the host's own immune response (Ferrandon, 2013;Medzhitov et al, 2012;Soares et al, 2017). For instance, the Immune Responsive Catalase IRC is induced by an immune challenge in a Toll-dependent manner and might be required in regulating a ROS response triggered by injury (Capilla et al, 2017;Nam et al, 2012). This however remains to be formally demonstrated in the framework of the systemic humoral immune response.…”