Meta-Analysis of Immune Induced Gene Expression Changes in Diverse Drosophila melanogaster Innate Immune Responses

Abstract

Organisms are commonly infected by a diverse array of pathogens and mount functionally distinct responses to each of these varied immune challenges. Host immune responses are characterized by the induction of gene expression, however, the extent to which expression changes are shared among responses to distinct pathogens is largely unknown. To examine this, we performed meta-analysis of gene expression data collected from Drosophila melanogaster following infection with a wide array of pathogens. We identified 62 genes that are significantly induced by infection. While many of these infection-induced genes encode known immune response factors, we also identified 21 genes that have not been previously associated with host immunity. Examination of the upstream flanking sequences of the infection-induced genes lead to the identification of two conserved enhancer sites. These sites correspond to conserved binding sites for GATA and nuclear factor κB (NFκB) family transcription factors and are associated with higher levels of transcript induction. We further identified 31 genes with predicted functions in metabolism and organismal development that are significantly downregulated following infection by diverse pathogens. Our study identifies conserved gene expression changes in Drosophila melanogaster following infection with varied pathogens, and transcription factor families that may regulate this immune induction.

Glucocerebrosidase deficiency leads to neuropathology via cellular immune activation

“…We detected 10,903 transcripts, of which 379 (3.5%) were significantly increased in abundance in Gba1b mutants, while 175 (1.6%) were decreased in abundance. The transcripts most strikingly increased in abundance in Gba1b mutants included multiple members of the Turandot family, a group of genes transcribed in response to immune threats and stressors [27, 28], and the Tep (thioester-containing protein) family (Fig 1A), which is orthologous to the mammalian complement system [29, 30]. Enrichment analysis with PANGEA [31] revealed that the transcripts increased in abundance in Gba1b mutants were strongly enriched for immune- and defense-related functions (Fig 1B-C).…”

“…See Materials and Methods for full details. The example is based on the marker list from the immune meta-analysis study [28], which includes 55 transcripts. (A) Chance-level overlap (no enrichment).…”

“…Our data sources included sets of transcriptional changes detected in response to fungi, bacteria, viruses, and parasitoids [33][34][35][36][37][38]. We also compared our RNA-Seq data to a set of 62 core genes responsive to immune challenge, derived from a meta-analysis of 12 pathogen challenge studies [28]. See Methods and Fig S1 for details of our analyses.…”

Hemocytes and fat body cells, the only professional immune cell types in Drosophila, show strikingly different responses to systemic infections

“…Several reasons might account for this. On the one hand, it is possible that there are significant differences in responses to infections with different pathogens, an aspect that is certainly important ( 38 , 39 ). On the other hand, these differences may also represent secondary effects that could be explained by different degrees of infection events and responses caused by them ( 40 , 41 ).…”