The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the...

Area of Science:

• Innate immunity
• Molecular mechanisms of host-pathogen interactions
• Drosophila melanogaster model system

Background:

• Innate immune systems detect pathogens via molecular patterns or functional features.
• Pattern recognition receptor (PRR) detection is well-studied, but sensing virulence factor activity is less understood.
• Drosophila Persephone protease is implicated in a danger pathway activating Toll signaling via proteolytic activity.

Purpose of the Study:

• To elucidate the activation mechanism and specificity of the Persephone-mediated danger pathway.
• To identify how Persephone senses pathogen virulence factors.

Main Methods:

• Identification of a unique protease-sensitive region in Persephone's pro-domain.
• Analysis of Persephone activation cascade.
• Characterization of Persephone's sensing capabilities.

Main Results:

• A unique bait region in Persephone's pro-domain is identified, acting as a universal sensor for exogenous proteases.
• Cleavage in this bait region initiates a sequential activation process, leading to Persephone maturation.
• Persephone is shown to sense a wide array of microbes via their virulence factor activities.

Conclusions:

• Persephone functions as an immune receptor, detecting microbial virulence factor activity directly.
• This mechanism broadens the understanding of innate immune sensing beyond conserved molecular patterns.
• The findings establish a novel pathway for innate immune recognition in Drosophila.