An Effector Peptide Family Required for Drosophila Toll-Mediated Immunity

Abstract

In Drosophila melanogaster, recognition of an invading pathogen activates the Toll or Imd signaling pathway, triggering robust upregulation of innate immune effectors. Although the mechanisms of pathogen recognition and signaling are now well understood, the functions of the immune-induced transcriptome and proteome remain much less well characterized. Through bioinformatic analysis of effector gene sequences, we have defined a family of twelve genes – the Bomanins (Boms) – that are specifically induced by Toll and that encode small, secreted peptides of unknown biochemical activity. Using targeted genome engineering, we have deleted ten of the twelve Bom genes. Remarkably, inactivating these ten genes decreases survival upon microbial infection to the same extent, and with the same specificity, as does eliminating Toll pathway function. Toll signaling, however, appears unaffected. Assaying bacterial load post-infection in wild-type and mutant flies, we provide evidence that the Boms are required for resistance to, rather than tolerance of, infection. In addition, by generating and assaying a deletion of a smaller subset of the Bom genes, we find that there is overlap in Bom activity toward particular pathogens. Together, these studies deepen our understanding of Toll-mediated immunity and provide a new in vivo model for exploration of the innate immune effector repertoire.

Antimicrobial defence and persistent infection in insects revisited

“…The number of AMPs discovered by both, proteomics and RNA-seq, is comparable to the number of AMPs in many other insect species [29]. Recently, a new group of very short AMPs was described in Drosophila dubbed Bomanins [30]. We could not find any evidence for the existence of this type of peptides either in our transcriptomic or in our proteomic data.…”

Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

“…, Peptidoglycan recognition protein SA (PGRP-SA) and Gram-negative binding protein-like 3 (GNBP-like3)] and genes that regulate the JAK-STAT pathway [ e.g. , Suppressor of cytokine signaling at 36E (Socs36E)] (De Gregorio et al 2001, 2002; Agaisse and Perrimon 2004; Lemaitre and Hoffmann 2007; Bier and Guichard 2012; Stec et al 2013; Chakrabarti et al 2014; Kurata 2014; Clemmons et al 2015). Also included were genes up-regulated by pathogen infection that control proteolysis, cell growth, and oxidative stress.…”

“…These data raise important questions: by what mechanisms do age and diet control transcription of Drs differently than other AMP genes and how might Drs function differently than other AMPs to inhibit mortality? The transcription mechanism is likely to involve the Toll pathway because Drs is predominantly regulated by the Toll pathway, as are secreted peptide-encoding genes in the Bom family that, like Drs, had age- and diet-regulated expression that negatively correlated with the MI 24 (Lemaitre and Hoffmann 2007; Clemmons et al 2015) (Table 2). The Drs-specific function may be related its ability to inactivate a voltage-gated sodium channel, since blocking upregulation of a sodium channel improves outcomes in a rat TBI model (Cohen et al 2009; Huang et al 2014).…”

The <b><i>Drosophila</i></b> Chitinase-Like Protein IDGF3 Is Involved in Protection against Nematodes and in Wound Healing

“…table S1: ctr infection-specific). They include 2 small peptides (immune-induced peptides, recently named Bomanins [24] ) and, most significantly, Drosomycin , the signature gene for the Toll pathway. The dataset from infected Idgf3 mutants allowed us to comprehensively identify those genes that are induced in an IDGF3-dependent manner upon EPN infections (online suppl.…”