"LA is different, and hopefully represents a kind of scientific publication machinery that removes the hurdles from free flow of scientific thought." Your paper will be: • Available to your entire community free of charge • Fairly and quickly peer reviewed • Yours! You retain copyright http://www.la-press.com Deconstructing host-pathogen interactions in Drosophila Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi) screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host. Drosophila has emerged as an important model for examining the function of genes that are relevant to diverse human diseases affecting a broad range of cell types (for reviews, see Bier, 2005; Bier and McGinnis, 2008) . Additionally, this model organism can serve as a host for a surprising variety of bacterial and viral pathogens. Seminal discoveries in the field of host-pathogen interactions have been made in Drosophila. For example, the Toll signaling pathway, which plays a central role in innate immunity, was first identified in Drosophila, and studies using this model organism have helped to identify and delineate fundamental conserved host genetic pathways involved in barrier formation and maintenance (Mace et al., 2005; Martin and Parkhurst, 2004; Pearson et al., 2009; Ting et al., 2005) , innate immune signaling (Agaisse and Perrimon, 2004; Dionne and Schneider, 2008; Ferrandon et al., 2007; Igaki et al., 2010; Ryu et al., 2010) , the RNA interference (RNAi) response (Sabin et al., 2010) , pathogen engulfment (Meister, 2004) , and the evolution of intracellular pathogens (Haselkorn, 2010; Serbus et al., 2008) . As discussed in detail below, Drosophila has also been used to identify and analyze the function of pathogen-derived virulence factors (Avet-Rochex et al., 2005; Avet-Rochex et al., 2007; Botham et al., 2008; Guichard et al., 2010; Guichard et al., 2006; Shelly et al., 2009; Guichard et al., 2011) .