The Drosophila immune deficiency (IMD) pathway, homologous to the mammalian tumor necrosis factor (TNF-alpha) signaling pathway, initiates antimicrobial peptide (AMP) production in response to infection by gram-negative bacteria. A membrane-spanning peptidoglycan recognition protein, PGRP-LC, functions as the receptor for the IMD pathway. This receptor is activated via pattern recognition and binding of monomeric peptidoglycan (DAP-type PGN) through the PGRP ectodomain. In this article, we show that the receptor PGRP-LC is down-regulated in response to Salmonella/Escherichia coli infection but is not affected by Staphylococcus infection in vivo, and an ectodomain-deleted PGRP-LC lacking the PGRP domain is an active receptor. We show that the receptor PGRP-LC regulates and integrates two host defense systems: the AMP production and melanization. A working model is proposed in which pathogen invasion and tissue damage may be monitored through the receptor integrity of PGRP-LC after host and pathogen are engaged via pattern recognition. The irreversible cleavage or down-regulation of PGRP-LC may provide an additional cue for the host to distinguish pathogenic microbes from nonpathogenic ones and to subsequently activate multiple host defense systems in Drosophila, thereby effectively combating bacterial infection and initiating tissue repair.

Systemically administered vectors must cross the endothelial lining of tumor blood vessels to access cancer cells. Vectors that interact with markers on the lumenal surface of these endothelial cells might have enhanced tumor localization. Here, we generated oncolytic measles viruses (MVs) displaying alpha(v)beta(3) integrin-binding peptides, cyclic arginine-glycine-aspartate (RGD) or echistatin, on the measles hemagglutinin protein. Both viruses had expanded tropisms, and efficiently entered target cells via binding to integrins, but also retained their native tropisms for CD46 and signaling lymphocyte activation molecule (SLAM). When fluorescently labeled and injected intravascularly into chick chorioallantoic membranes (CAMs), in contrast to unmodified viruses, the integrin-binding viral particles bound to the lumenal surface of the developing chick neovessels and infected the CAM vascular endothelial cells. In a mouse model of VEGF-induced angiogenesis in the ear pinna, the integrin-binding viruses, but not the parental virus, infected cells at sites of new blood vessel formation. When given intravenously to mice bearing tumor xenografts, the integrin-binding virus infected endothelial cells of tumor neovessels in addition to tumor parenchyma. To our knowledge, this is the first report demonstrating that oncolytic MVs can be engineered to target the lumenal endothelial surface of newly formed blood vessels when administered intravenously in living animals.