A serpin mutant links Toll activation to melanization in the host defence of Drosophila

Abstract

A prominent response during the Drosophila host defence is the induction of proteolytic cascades, some of which lead to localized melanization of pathogen surfaces, while others activate one of the major players in the systemic antimicrobial response, the Toll pathway. Despite the fact that gain‐of‐function mutations in the Toll receptor gene result in melanization, a clear link between Toll activation and the melanization reaction has not been firmly established. Here, we present evidence for the coordination of hemolymph‐borne melanization with activation of the Toll pathway in the Drosophila host defence. The melanization reaction requires Toll pathway activation and depends on the removal of the Drosophila serine protease inhibitor Serpin27A. Flies deficient for this serpin exhibit spontaneous melanization in larvae and adults. Microbial challenge induces its removal from the hemolymph through Toll‐dependent transcription of an acute phase immune reaction component.

Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia

“…In Drosophila, there are 29 serpins, and the precise functions of most of them are not well understood (19). Several fly serpins regulate the Toll pathway as loss of activities in Spn43Ac, Spn-27A, and Spn77Ba lead to the activation of this important signaling pathway (30,31,37,38). Our findings show that secreted Spn5 also regulates the Toll pathway, apparently by controlling the proteolytic processing of Spaetzle.…”

“…Activation of Toll pathway could lead to the initiation of the melanization cascade (31). De novo synthesis of melanin in response to tissue damage occurs through the melanization cascade, a series of enzymatic reactions involving serine proteases that activate phenol oxidase (PO), which catalyzes the conversion of phenolic substrates to quinones, which then polymerize to form melanin (32).…”

Peptidoglycan Recognition Proteins Involved in 1,3-β-D-Glucan-dependent Prophenoloxidase Activation System of Insect

“…The soluble proteins of plasma, hemocyte lysate, and fat body were precipitated with trichloroacetic acid and subjected to SDS-PAGE and then immunoblotting with affinity-purified Hd-PGRP-1 and Hd-PGRP-2 antibodies, respectively. Previously it was reported that insect proPO system induced the activation of serine protease zymogen to active serine protease during 1,3-␤-D-glucan-dependent proPO activation (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)30). To explore the existence of serine protease activity during 1,3-␤-D-glucan-specific proPO activation, we examined the amidase activity in the presence of 1,3-␤-D-glucan and Ca 2ϩ by using commercially available trypsin substrate, Boc-PheSer-Arg-MCA.…”

“…This enzyme produces toxic compounds to microorganisms by oxidizing phenols to melanin, and it also participates in the sclerotization of the cuticle, which is vital for the survival of insects (18). Many reports have been published about the proPO of the invertebrate and its activation mechanism (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). A key question regarding the proPO activation system is how pattern recognition molecules can induce activation of the system in response to microbial infection.…”

Histological Observation and Expression Patterns of antimicrobial peptides during Fungal Infection in Musca domestica (Diptera: Muscidae) Larvae

“…A great number of immune regulators are involved in these processes, including serine proteinase inhibitors (Serpin). In Tenebrio molitor (Jiang et al 2009) and D. melanogaster (Ligoxygakis et al 2002;Fullaondo et al 2011), serpins can regulate the immune response through the Toll signal pathway and prophenoloxidase-activating system. Li discovered at least 11 serpins in housefly, including a gene homologous to serpin27A of D. melanogaster .…”