Evolution of immune systems during invasion

It goes without saying, perhaps, that your immune system is important to you. Without it, you'd rapidly be consumed by bacteria and fungus, and in the short while it took for these to kill you, viruses would be raging out of control, and worms would be having a field day. Your immune system is important.

Your immune system is also immensely complex. When you scratch yourself and admit a few bacteria to your bloodstream, an astonishing cascade of events occur that detect the intruders, attack them, and then clean up the unholy mess. This kind of clean up operation is usually handled by the innate arm of the immune system; most unwanted guests are annihilated by the general-purpose tools in this arsenal. Occasionally, however, something gets into your body that has ways around these generic defences. When your innate system is not coping with such an invader (and the system detects this automatically), it calls in the cavalry: the acquired immune system. This arm of the immune system has a vast library of randomly-generated keys; it finds a key that works for identifying the particular invader, and then sends to the workshop to have millions and millions of this particular key made up. A few days after the invader arrives, these keys are everywhere, all the invaders are flagged for disposal, and dealt with mercilessly. All of this happens without any conscious effort on your behalf. This complex system, with massively redundant and astonishingly flexible defences takes care of business for you.

So the immune system is critically important, and very complex. It's also expensive to run; not in the currency we usually associate with defence spending -- money -- but in the currency of energy. The immune system involves many many cells of many different types, communicating and coordinating the action with a dizzying array of communication molecules. It takes energy to run this thing. But if it isn't running well, you stand a good chance of being killed: either by a pathogen, or by your immune system itself (think of the various auto-immune diseases that afflict humans). Suffice to say, the immune system is under strong selection for operating optimally.

Now, throw in a period of range advance; the kind of thing that happens when an invasive species spreads, or a native species shifts in response to climate change. All sorts of strange things happen on these invasion fronts. One of the things that happens is that evolutionary forces conspire to force dispersal to evolve to very high levels. Invasion front individuals will tend to invest a lot in dispersal. This investment is an investment of energy: dispersal takes effort. Where might individuals take energy from so as to invest it in dispersal? One distinct possibility is that they might take it from the immune system.

Ok, so hang on a minute. We've just established that the immune system is very important, how could we imagine getting away with lowered investment in immunity? Well, another weird thing that happens on invasion fronts is that rates of infection with parasites and pathogens is also low. Why so? Two reasons. First, chance: because so few individuals make up the invasion front in any given generation it is entirely possible that these few individuals just don't happen to be carrying parasite X. Parasite X will find it very hard to catch up with the invasion front thereafter, particularly if having parasite X has consequences for dispersal or fitness. A second reason is that many parasites and pathogens have higher transmission rates at high host density. Host density is, by definition, low on the host's invasion front: so lower rates of transmission may also conspire to have parasites and pathogens lagging behind an invasion front. In short, yes, the immune system is critically important, but it might not need to be quite so formidable on an invasion front. The relative scarcity of parasites and pathogens on the invasion front may give populations evolutionary wriggle room to lower their immune investment.

How might we expect the immune system to change then, on an invasion front? Well, here's where we run into a bit of trouble. The immune system is very complex. The immune system makes the Large Hadron Collider look like the work of unimaginative two-year-olds. It's almost impossible to know what the costs of each bit of the immune system are and how we might change the system's function when we turn its various dials. It might sound like a bit of a cop out, but predicting how, exactly, the immune system might change seems foolish. But to predict that it will change, in some way, seems sensible. Greg Brown, Rick Shine, and myself set out to test exactly this proposition.

Testing the idea of an immune system that changes during invasion took time. We had to collect toads from across northern Australia: sampling from the invasion front to long-established populations. We bred these animals and raised their offspring so that we could be more certain that any differences we observed were evolved shifts rather than developmental differences arising from growing up in different places. Finally we (and by 'we', I mean Greg) had to develop and meticulously test various assays of immune function. Once we dispensed with those three years of effort, we found substantial shifts in the immune system between invasion front and older populations.

Although we weren't really wanting to make predictions about which bits of the immune system should shift and in what direction, our results in this regard were nonetheless surprising. Toads from the invasion front seem to invest more in their innate immune system than their counterparts in the range core. Invasion front toads produce more neutrophils (a type of white blood cell) and have blood with higher bacterial killing capacity than their more sedentary relatives. Other aspects that we (i.e., Greg) measured -- things like their stress response, and their acquired immune system's response to a foreign antigen -- showed no real shift with invasion history. So much for the idea that the invaders should be investing less in their immune system!

Instead, our results seem to suggest that toads are investing more in a couple of key areas of their immune system. Intriguingly, other work by Greg showed that these same areas of the immune system become suppressed in individuals that disperse long distances. Thus it looks like the invasion front toads are actually investing more in these aspects of the immune system to compensate for the fact that they will suppress these aspects in the act of moving large distance every night. The evolved shifts we observed appear to be compensatory in nature.

So the imune system is important, and toads seem to be trying to maintain its status quo despite the stress and rigours of long distance dispersal. That's pretty interesting. But can we throw out the hypothesis that they should invest less in the immune system? Well, we found no evidence to support the idea, so that's not encouraging, but we may simply also have looked in the wrong places (have I mentioned how complex the immune system is?). For now I'd say the Jury is still out: we'll have to wait for other studies, on different species and different aspects of the immune system, before burying the idea for good.