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Background Members of the thioester-containing protein (TEP) family contribute to host defence in both insects and mammals. However, their role in the immune response of Drosophila is elusive. In this study, we address the role of TEPs in Drosophila immunity by generating a mutant fly line, referred to as TEPq Δ, lacking the four immune-inducible TEPs, TEP1, 2, 3 and 4. Results Survival analyses with TEPq Δ flies reveal the importance of these proteins in defence against entomopathogenic fungi, Gram-positive bacteria and parasitoid wasps. Our results confirm that TEPs are required for efficient phagocytosis of bacteria, notably for the two Gram-positive species tested, Staphylococcus aureus and Enterococcus faecalis. Furthermore, we show that TEPq Δ flies have reduced Toll pathway activation upon microbial infection, resulting in lower expression of antimicrobial peptide genes. Epistatic analyses suggest that TEPs function upstream or independently of the serine protease ModSP at an initial stage of Toll pathway activation. Conclusions Collectively, our study brings new insights into the role of TEPs in insect immunity. It reveals that TEPs participate in both humoral and cellular arms of immune response in Drosophila. In particular, it shows the importance of TEPs in defence against Gram-positive bacteria and entomopathogenic fungi, notably by promoting Toll pathway activation. Electronic supplementary material The online version of this article (doi:10.1186/s12915-017-0408-0) contains supplementary material, which is available to authorized users.

Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses. Furthermore, through functional genetic screening, bioinformatic analyses and yeast one-hybrid screening, we determined that the transcription factors Scalloped (Sd), Mothers against dpp (Mad), and D-Fos are principal regulators of upd3 expression. Our study demonstrates that upd3 transcription in the gut is regulated by the activation of multiple pathways, including the Hippo, TGF-β/Dpp, and Src, as well as p38-dependent MAPK pathways. Thus, these essential pathways, which are known to control ISC proliferation cell-autonomously, are also activated in ECs to promote tissue turnover the regulation of upd3 transcription., Author summary Tissue regeneration is a fundamental process that maintains the integrity of the intestinal epithelium when faced with chemical or microbial stresses. In both healthy and diseased conditions, pro-regenerative cytokines function as central coordinators of gut renewal, linking inflammation to stem cell activity. In Drosophila, the upstream events that stimulate the production of the primary cytokine Unpaired 3 (Upd3) in response to indigenous or pathogenic microbes have yet to be elucidated. In this study, we demonstrate that upd3 expression is driven in different cell types by separate microbe-responsive enhancers. In enterocytes (ECs), cytokine induction relies on the Yki/Sd, Mad/Med, and AP-1 transcription factors (TFs). These TF complexes are activated downstream of the Hippo, TGF-β and Src-MAPK pathways, respectively. Inhibiting these pathways in ECs impairs upd3 transcription, which in turn blocks intestinal stem cell proliferation and reduces the survival rate of adult flies following enteric infections. Altogether, our study identifies the major microbe-responsive enhancers of the upd3 gene and sheds light on the complexity of the gene regulatory network required in ECs to regulate tissue homeostasis and stem cell activity in the digestive tract.