Evolutionary immunology to explore original antiviral strategies

Abstract

Over the past 25 years, the field of evolutionary developmental biology (evo–devo) has used genomics and genetics to gain insight on the developmental mechanisms underlying the evolution of morphological diversity of animals. Evo–devo exploits the key insight that conserved toolkits of development (e.g. Hox genes) are used in animals to produce genetic novelties that provide adaptation to a new environment. Like development, immunity is forged by interactions with the environment, namely the microbial world. Yet, when it comes to the study of immune defence mechanisms in invertebrates, interest primarily focuses on evolutionarily conserved molecules also present in humans. Here, focusing on antiviral immunity, we argue that immune genes not conserved in humans represent an unexplored resource for the discovery of new antiviral strategies. We review recent findings on the cGAS-STING pathway and explain how cyclic dinucleotides produced by cGAS-like receptors may be used to investigate the portfolio of antiviral genes in a broad range of species. This will set the stage for evo–immuno approaches, exploiting the investment in antiviral defences made by metazoans over hundreds of millions of years of evolution. This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.

When the microbiome shapes the host: immune evolution implications for infectious disease

“…Innate immune signalling therefore passes information through bottlenecks: a few broadly conserved MAMPs activate the cascades that are present, and these cascades converge on just one or a few TFs. This bottleneck regulatory approach is also part of the hourglass model of ‘evo-devo’ and ‘evo-immuno’ dynamics, discussed in [ 11 ]—in immunology, they may reflect a trade-off between producing a rapid defence or a specific one ( box 1 ).…”

Sculpting the microbiome

“…Reflecting on host–virus interactions, Imler et al . [ 2 ] next synthesize recent work which has shown that even closely related species have distinct immune response profiles. Drawing a parallel from the hourglass model of evolutionary development (evo-devo), Imler et al .…”

“…Drawing a parallel from the hourglass model of evolutionary development (evo-devo), Imler et al . [ 2 ] describe ‘evo-immuno' dynamics. These dynamics act across multiple levels, from receptors to core signalling elements, which themselves regulate diverse effectors.…”

Investigating the Evolution of Drosophila STING-Dependent Antiviral Innate Immunity by Multispecies Comparison of 2′3′-cGAMP Responses

“…One caveat of this approach is that it overlooks biodiversity and the fact that during the never-ending arms race between hosts and viruses, diversification of the portfolio of antiviral defenses is expected to occur in the hosts ( Daugherty and Malik 2012 ; Goodin et al 2016 ; McDougal et al 2022 ). When it comes to biodiversity, insects with their 1.2 million known species are unmatched, offering the opportunity to extend the repertoire of antiviral genes ( Jactel et al 2021 ; Imler et al 2024 ).…”

“…The discovery that injection of CDNs into flies induces a potent transcriptional response associated with antiviral protection provides a powerful means to identify antiviral genes in Drosophila , without the caveat of the stress reactions triggered by cell lysis or tissue damage associated with viral infection. This paves the way for evolutionary immunology studies aimed at comparing the repertoire of antiviral genes in different species ( Imler et al 2024 ). Here, we exploit the CDN STING-agonist injection assay to explore the evolution of STING-dependent antiviral immunity in 10 different Drosophila species.…”