The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll-pathway activation function.
The Drosophila Toll-signaling pathway controls the systemic antifungal host response. Gram-negative binding protein 3 (GNBP3), a member of the beta-glucan recognition protein family senses fungal infections and activates this pathway. A second detection system perceives the activity of proteolytic fungal virulence factors and redundantly activates Toll. GNBP3(hades) mutant flies succumb more rapidly to Candida albicans and to entomopathogenic fungal infections than WT flies, despite normal triggering of the Toll pathway via the virulence detection system. These observations suggest that GNBP3 triggers antifungal defenses that are not dependent on activation of the Toll pathway. Here, we show that GNBP3 agglutinates fungal cells. Furthermore, it can activate melanization in a Toll-independent manner. Melanization is likely to be an essential defense against some fungal infections given that the entomopathogenic fungus Beauveria bassiana inhibits the activity of the main melanization enzymes, the phenol oxidases. Finally, we show that GNBP3 assembles "attack complexes", which comprise phenoloxidase and the necrotic serpin. We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing effector molecules in direct contact with the invading microorganisms.
Matskevich
Alexey A
AA
Equipe Fondation Recherche Médicale, UPR 9022 du CNRS, Université de Strasbourg Institut de Biologie Moléculaire et Cellulaire, Strasbourg Cedex, France.
Quintin
Jessica
J
Ferrandon
Dominique
D
D000371:Agglutination; D000818:Animals; D052982:Beauveria / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology* / Q000494:pharmacology; D029721:Drosophila Proteins / Q000276:immunology* / Q000494:pharmacology / Q000502:physiology; D004331:Drosophila melanogaster / Q000276:immunology* / Q000382:microbiology; D004789:Enzyme Activation; D005658:Fungi / Q000276:immunology*; D006458:Hemolymph / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins / Q000502:physiology*; D014442:Monophenol Monooxygenase / Q000502:physiology; D046912:Multiprotein Complexes / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015843:Serpins / Q000502:physiology; D013172:Spores, Fungal; D051193:Toll-Like Receptors / Q000276:immunology
D002352:Carrier Proteins; D029721:Drosophila Proteins; C516487:GNBP3 protein, Drosophila; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D046912:Multiprotein Complexes; D011993:Recombinant Fusion Proteins; D015843:Serpins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C417282:nec protein, Drosophila; C086179:spz protein, Drosophila; D014442:Monophenol Monooxygenase