The surprisingly complex immune gene repertoire of a simple sponge, exemplified by the NLR genes: A capacity for specificity?

•The diverse relationships between animals and microbes require a sophisticated innate immune system to discriminate friend from foe.•NLRs respond to a broad spectrum of microbial ligands and likely play a central role in animal–bacterial conversations.•The morphologically simple coral reef sponge Amphimedon queenslandica has a remarkably large and diverse suite of NLR genes and a large number of potential adaptor and effector proteins.•These genomic features suggest a sophisticated NLR-based immune specificity that may have originated at the dawn of the animal kingdom more than 600 million years ago. Most bacteria are not pathogenic to animals, and may instead serve beneficial functions. The requisite need for animals to differentiate between microbial friend and foe is likely borne from a deep evolutionary imperative to recognise self from non-self, a service ably provided by the innate immune system. Recent findings from an ancient lineage of simple animals – marine sponges – have revealed an unexpectedly large and diverse suite of genes belonging to one family of pattern recognition receptors, namely the NLR genes. Because NLRs can recognise a broad spectrum of microbial ligands, they may play a critical role in mediating the animal–bacterial crosstalk needed for sophisticated discrimination between microbes of various relationships. The building blocks for an advanced NLR-based immune specificity encoded in the genome of the coral reef sponge Amphimedon queenslandica may provide a specialisation and diversity of responses that equals, or even exceeds, that of vertebrate NLRs.