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.
Highlights
Constant interaction with microbes is a fact of life, and sometimes death, for animals
Dedicated defense systems in the bodies of humans and other animals protect against dangerous microbes, such as bacteria and fungi
As in humans, protective activities are triggered when fragments of bacteria or fungi activate a system for defense gene regulation known as the Toll signaling pathway
Summary
Constant interaction with microbes is a fact of life, and sometimes death, for animals. Many microbes are neutral or beneficial to the host’s health. Some are pathogenic and threaten the host’s viability. In vertebrates and invertebrates alike, immune responses are initiated by recognition of pathogen associated molecular patterns (PAMPs) following invasion of host tissues [1, 2]. This recognition of conserved microbial products triggers innate immune signaling pathways that are closely related in species as divergent as flies and humans [3,4,5]. Pathway activation initiates a transcriptional program encoding an array of effector peptides and proteins
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