A time course transcriptomic analysis of host and injected oncogenic cells reveals new aspects of Drosophila immune defenses

Abstract

Oncogenic RasV12 cells [A. Simcox et al., PLoS Genet. 4, e1000142 (2008)] injected into adult males proliferated massively after a lag period of several days, and led to the demise of the flies after 2 to 3 wk. The injection induced an early massive transcriptomic response that, unexpectedly, included more than 100 genes encoding chemoreceptors of various families. The kinetics of induction and the identities of the induced genes differed markedly from the responses generated by injections of microbes. Subsequently, hundreds of genes were up-regulated, attesting to intense catabolic activities in the flies, active tracheogenesis, and cuticulogenesis, as well as stress and inflammation-type responses. At 11 d after the injections, GFP-positive oncogenic cells isolated from the host flies exhibited a markedly different transcriptomic profile from that of the host and distinct from that at the time of their injection, including in particular up-regulated expression of genes typical for cells engaged in the classical antimicrobial response of Drosophila.

Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila

“…Our laboratory in Strasbourg recently conducted a study focused on the response of drosophila adult flies to oncogenic RasV12-expressing cells injected into the body cavity [ 70 ]. Eleven days after injection, we noticed that numerous immune-induced genes were activated.…”

“…The PGRP family of proteins is subdivided into two categories: some, such as PGRP-LC or PGRP-LE, bind the ligand, whereas others, such as PGRP-SC and PGRP-LB, are amidase enzymes that cleave the ligand and are unable to activate the pathway [ 70 ]. This second class of molecules is involved in eliminating a moderate amount of PGN, which is important for immune tolerance to commensal bacteria in the gut.…”

Single Cell Analysis of the Fate of Injected Oncogenic RasV12 Cells in Adult Wild Type <i>Drosophila</i>

“…A previous report from our group, based on the same immortalized cell line which we use here, and performed in the same experimental setting, had pointed to major differences between antimicrobial defenses and reactions against homologous OCs [20] . Here, we extend these data by using single-cell transcriptomics of the injected cells at the time of injection into the flies and after allowing for proliferation for 11 days in the host.…”

“…The injected RasV12 oncogenic cell (OC) line which we used here and in our previous study [20] is a tumor cell line of embryonic origin, constructed by A. Simcox and colleagues in 2008 through introducing an oncogenic form of Ras (RasV12, carrying the Val/Gly mutation) into Drosophila embryos under a constitutive Actin 5C promoter which also controls expression of the gene encoding the reporter GFP. The transgenic cells were isolated by these authors and continuously passaged over 20 generations for immortalization [18] .…”

Continuous muscle, glial, epithelial, neuronal, and hemocyte cell lines for Drosophila research

“…These advances are accompanied by the availability of several distinct mammalian cell lines derived from different tissue types. Similarly, the use of insect cell lines also complements whole organismal studies and helped to illuminate many aspects of insect cell biology (Luhur et al, 2019) including development (Sato & Siomi, 2020), immunity (Chen et al, 2021; Goodman et al, 2021), host-pathogen relationships (Smagghe et al, 2009), in addition to biotechnological applications (Hong et al, 2022).…”