Two Proteases Defining a Melanization Cascade in the Immune System of Drosophila

Abstract

The melanization reaction is used as an immune mechanism in arthropods to encapsulate and kill microbial pathogens. In Drosophila, the serpin Spn27A regulates melanization apparently by inhibiting the protease that activates phenoloxidase, the key enzyme in melanin synthesis. Here, we have described the genetic characterization of two immune inducible serine proteases, MP1 and MP2, which act in a melanization cascade regulated by Spn27A. MP1 is required to activate melanization in response to both bacterial and fungal infection, whereas MP2 is mainly involved during fungal infection. Pathogenic bacteria and fungi may therefore trigger two different melanization cascades that use MP1 as a common downstream protease to activate phenoloxidase. We have also shown that the melanization reaction activated by MP1 and MP2 plays an important role in augmenting the effectiveness of other immune reactions, thereby promoting resistance of Drosophila to microbial infection.

Manduca sexta Hemolymph Proteinase 21 Activates Prophenoloxidase-activating Proteinase 3 in an Insect Innate Immune Response Proteinase Cascade

“…activates proPO in response to bacteria and fungi and one that responds just to fungi (15). Likewise, RNA interference studies indicate that more than one melanization pathway is induced in response to infection in A. gambiae (11,14).…”

Broad-spectrum antimicrobial activity of the reactive compounds generated in vitro by Manduca sexta phenoloxidase

“…However, since over 100 immunity-related genes were affected in these Toll pathway mutants (De Gregorio et al, 2002b), it is perhaps inappropriate to use those as references to assess the contribution of melanization. During the preparation of this paper, we noticed that Tang et al (2006) further evaluated the roles of Drosophila MP2 (i.e. PAE1) and MP1 in melanization.…”

Persephone/Spätzle Pathogen Sensors Mediate the Activation of Toll Receptor Signaling in Response to Endogenous Danger Signals in Apoptosis-deficient Drosophila

“…We still believe that this prominent immune pathway could benefit the animals in a way that prepares them for upcoming tissue damage, for instance, by increasing the hemocytes whose function is crucial in sequestering large debris and relaying signals that are required in tissue repair. Melanization has been shown under certain circumstances to enhance the effectiveness of defense signaling upon a life-threatening stimulus (53). Thus, we think that the activation of Toll would have some beneficial roles in apoptosis-deficient organisms.…”