Abstract
BackgroundMembers 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 TEPqΔ, lacking the four immune-inducible TEPs, TEP1, 2, 3 and 4.ResultsSurvival analyses with TEPqΔ 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 TEPqΔ 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.ConclusionsCollectively, 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.
Highlights
Members of the thioester-containing protein (TEP) family contribute to host defence in both insects and mammals
Consistent with previous microarray data [18], Western blot on haemolymph samples using an anti-green fluorescent protein (GFP) antibody reveals a significant increase in the amount of TEP2-GFP at 4 h and 48 h after septic injury with the fungus B. bassiana (Fig. 1a, left panel)
These experiments are consistent with the notion that TEP2 and TEP4 are secreted into the haemolymph and undergo proteolytic cleavage upon infection, to what was reported for A. gambiae TEP1 [9]
Summary
Members of the thioester-containing protein (TEP) family contribute to host defence in both insects and mammals. Their role in the immune response of Drosophila is elusive. Results: Survival analyses with TEPqΔ flies reveal the importance of these proteins in defence against entomopathogenic fungi, Gram-positive bacteria and parasitoid wasps. We show that TEPqΔ 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. Upon recognition of invading microbes, several arms of innate defence are activated and coordinated in order to mount an appropriate immune response and resolve infection. In addition to the systemic immune response that takes place in the haemolymph, epithelia that are in contact with the external environment contribute to the local immune response by producing ROS and antimicrobial peptides
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