ISC proliferation and parasite infection.

ISC proliferation dynamics following H.muscarum infection at 6h (A), Day 1 (B) and Day 2 (C) post-challenge; the parasite was able to suppress ISC proliferation in the absence of Relish (6h, D1 and D3) and to a lesser extend Imd (6h). (D) Relish also played a role in the proliferation of ISCs as loss of Relish blocked ISC proliferation (PH3-red channel) following parasite challenge while (E) Relish overexpression induced ISC proliferation even in the absence of the parasite (see PH3 in sucrose control) (F) A cartoon illustrating a working model of the H. muscarum oral infection model in Drosophila. Both STAT and Relish transcription factors are essential for ISC proliferation and differentiation whereas Toll signaling as well as ROS generation (through Duox) is important in ECs. Parasite infection can also induce Relish-dependent transcription as seen in the upregulation of IMD controlled AMPs. Our hypothesis is that the combinatorial effect from STAT-mediated signaling and Relish-dependent transcription encourages a hyper proliferation of ISCs which eventually results in a fast epithelium turn over in the Drosophila gut. Such a mechanism, together with the expression of effector molecules like AMPs and ROS would be able to remove the parasite quickly and efficiently. Two-way ANOVA was used to analyse all data (*p<0.01, **p<0.001, ***p<0.0001).