The ability to thwart infection is one of the most remarkable inventions in animal evolution. But despite its importance, immunity does not work the same way in all animals. Whereas vertebrate adaptive immunity has memory and specificity, meaning that it can use a first encounter with a pathogen to arm itself against subsequent encounters with the same pathogen, invertebrates, like insects, lack this capacity – or so it was thought. Recent evidence supports the idea that invertebrate immunity is far more sophisticated than had been believed, even showing evidence for memory and specificity. But how does immunity evolve, and can it improve?
An international team of scientists led by Joachim Kurtz from the University of Münster, Germany, recently addressed this question. Kevin Ferro, now at the University of Arizona, USA, and Robert Peuß, now at the Stowers Institute in Kansas City, USA, conducted an experiment where they exposed flour beetles (Tribolium castaneum) to different bacterial pathogens and studied how their ability to overcome infection evolved over many generations. Their design was based on a procedure called ‘immune priming’ where beetle larvae are first injected with heat-killed bacteria and then subsequently challenged with a potentially lethal infection of the same or a different bacterial species later in life.
The logic of the experiment was simple. If immune priming induced immune memory, larvae would be protected during their second exposure to the same pathogen. This, in turn, would allow them to survive to adulthood and to breed the next generation of larvae, which, over several generations, would select for beetles with an improved ability to beat infection. In other words, they would experimentally evolve beetles with enhanced adaptive immunity.
After only 14 generations, and nearly 50,000 animals, it worked! The beetles evolved increased survival after priming and challenge. More impressively, the magnitude of this improvement was higher if each generation of larvae were primed and challenged with the same pathogen, a so-called specific challenge, than with a mismatched pair of pathogens, an unspecific challenge. In short, memory and specificity evolved readily. But how did it occur?
To identify mechanisms underlying enhanced immunity, the research team compared the gene expression profiles of primed beetles that evolved with a specific challenge each generation with those evolved with an unspecific challenge. Unsurprisingly, there were hundreds of differences between the groups. And while there were no diagnostic genes that simply explained improved immunity on their own, there were several tantalizing targets in well-known immune effectors that were significantly up- or down-regulated in the specific group, including genes for antimicrobial peptides and iron capture. Notably, several of these pathways serve crucial functions in vertebrate immunity, suggesting striking conservation of the mechanisms of pathogen defence across animals.
Beetles are hugely diverse, so much so that the 19th century biologist J. B. S. Haldane once quipped that God must have had an ‘inordinate fondness for beetles’. One can only imagine how Haldane would have reacted had he known about the massive numbers and incredible diversity of bacteria. Beetles, indeed all creatures, face unpredictable challenges from the innumerable quantities of microbes that they encounter at every stage of their lives. Most microbes are harmless, but if left unchecked by an active and flexible immune system that can respond to novel challenges, even these species would surely kill us. Although I'm excited by the cleverness and scope of this experiment, I'm not remotely surprised at the outcome. The massive success of beetles virtually guaranteed the result, at least in broad strokes. Figuring out how it all works promises many exciting discoveries to come.
