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Buchon, Nicolas,Poidevin, Mickael,Kwon, Hyun-Mi,Guillou, Auré,lien,Sottas, Valentin,Lee, Bok-Luel,Lemaitre, Bruno National Academy of Sciences 2009 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.106 No.30
<P>The Drosophila Toll receptor does not interact directly with microbial determinants, but is instead activated by a cleaved form of the cytokine-like molecule Spätzle. During the immune response, Spätzle is processed by complex cascades of serine proteases, which are activated by secreted pattern-recognition receptors. Here, we demonstrate the essential role of ModSP, a modular serine protease, in the activation of the Toll pathway by gram-positive bacteria and fungi. Our analysis shows that ModSP integrates signals originating from the circulating recognition molecules GNBP3 and PGRP-SA and connects them to the Grass-SPE-Spätzle extracellular pathway upstream of the Toll receptor. It also reveals the conserved role of modular serine proteases in the activation of insect immune reactions.</P>
The <i>Drosophila</i> Amidase PGRP-LB Modulates the Immune Response to Bacterial Infection
Zaidman-Ré,my, Anna,Hervé,, Mireille,Poidevin, Mickael,Pili-Floury, Sé,bastien,Kim, Min-Sung,Blanot, Didier,Oh, Byung-Ha,Ueda, Ryu,Mengin-Lecreulx, Dominique,Lemaitre, Bruno Elsevier 2006 Immunity Vol.24 No.4
<P><B>Summary</B></P><P>The <I>Drosophila</I> host defense against gram-negative bacteria is mediated by the Imd pathway upon sensing of peptidoglycan by the peptidoglycan recognition protein (PGRP)-LC. Here we report a functional analysis of PGRP-LB, a catalytic member of the PGRP family. We show that PGRP-LB is a secreted protein regulated by the Imd pathway. Biochemical studies demonstrate that PGRP-LB is an amidase that specifically degrades gram-negative bacteria peptidoglycan. In agreement with its amidase activity, PGRP-LB downregulates the Imd pathway. Hence, activation of PGRP-LB by the Imd pathway provides a negative feedback regulation to tightly adjust immune activation to infection. Our study also reveals that PGRP-LB controls the immune reactivity of flies to the presence of ingested bacteria in the gut. Our work highlights the key role of PGRPs that encode both sensors and scavengers of peptidoglycan, which modulate the level of the host immune response to the presence of infectious microorganisms.</P>