Population-level variation in parasite resistance due to differences in immune initiation and rate of response

A new study pub­lished in Evol­u­tion Let­ters uses an exper­i­ment­al approach to provide new insights into the evol­u­tion of para­site res­ist­ance across pop­u­la­tions. Author Dr. Aman­da Hund tells us more.

Para­sites and patho­gens are a com­mon and power­ful force in the nat­ur­al world, a fact many of us know all too well in the middle of a glob­al pan­dem­ic. It has long intrigued bio­lo­gists that some hosts are able to res­ist para­site infec­tions while oth­ers remain highly sus­cept­ible. Even among closely related pop­u­la­tions of the same spe­cies, the abil­ity to fight off a para­site often var­ies dra­mat­ic­ally. Because para­sites can reduce sur­viv­al and repro­duc­tion, this can have import­ant evol­u­tion­ary con­sequences. Yet, our under­stand­ing of the details of how para­site res­ist­ance evolves is still lim­ited. To tackle this import­ant ques­tion, it is use­ful to think about the inter­ac­tion between a host and a para­site as a series of sequen­tial steps. First, the host must encounter a para­site (expos­ure). Next the host must recog­nize that it is infec­ted and ini­ti­ate the right immune response. Then, the host must be able to carry out that response to a high enough level to kill or at least slow down the para­site. Finally, because immune responses are costly, once the host has cleared an infec­tion it must be able to turn off that response. Determ­in­ing where res­ist­ant and sus­cept­ible pop­u­la­tions dif­fer in that timeser­ies of events can help us fig­ure out where evol­u­tion is occur­ring between hosts and parasites.

Around 11,000 years ago, mar­ine dwell­ing threespine stickle­back fish took advant­age of newly uncovered lakes as the Pleis­to­cene gla­ciers melted along the west coast of Canada on Van­couver Island. While these lakes turned out to be a pretty good place to live, the fish were faced with a dan­ger­ous new para­site- a fresh­wa­ter tape­worm that infects the abdo­men of the fish and can grow to be over half its body weight. When full grown, this tape­worm can make it dif­fi­cult to swim or repro­duce and even manip­u­lates the fish’s beha­vi­or to increase the odds that it will be eaten by a bird, where the tape­worm repro­duces. Today, some lake pop­u­la­tions of stickle­back are still heav­ily infec­ted with large tape­worms, but oth­ers have evolved the abil­ity to res­ist­ant the tape­worm by encas­ing it in fibrous scar tis­sue, called fibrosis. These fish can pre­vent the tape­worm from grow­ing and some­times even kill it by trap­ping it in fibrosis. This is par­tic­u­larly inter­est­ing because fibrosis also occurs in humans, where it con­trib­utes to a wide vari­ety of dis­eases. The ques­tion of how fibrosis stim­u­la­tion, sever­ity, and recov­ery, may evolve is thus both fun­da­ment­al to our under­stand­ing evol­u­tion­ary diver­si­fic­a­tion, and may have applied bene­fits to under­stand human dis­ease as well.

We com­pared a res­ist­ant lake pop­u­la­tion, a sus­cept­ible lake pop­u­la­tion, and an ances­tral mar­ine pop­u­la­tion of fish to fig­ure out how this res­ist­ance has evolved. We used an exper­i­ment to tease apart the dif­fer­ent steps in the host response to the tape­worm to fig­ure out how these pop­u­la­tions dif­fer from one anoth­er. We injec­ted four dif­fer­ent immune chal­lenges into the abdo­men of fish and tracked their fibrosis response through time. These included 1) a saline con­trol, 2) alum, which is a gen­er­al immune stim­u­lant com­monly used in vac­cines, 3) tape­worm pro­tein which we extrac­ted from ground up tape­worms, and 4) a com­bin­a­tion of alum and tape­worm pro­tein. We did this exper­i­ment in lab raised fish from each pop­u­la­tion, to ensure that any dif­fer­ences we found were due to evol­u­tion and not just because of eco­lo­gic­al vari­ation between lakes.

We found that with enough time, all three pop­u­la­tions were able to mount a strong fibrosis response to the alum treat­ments, mean­ing their abil­ity to pro­duce fibrosis was uni­ver­sal. How­ever, only the res­ist­ant pop­u­la­tion was able to pro­duce fibrosis to the tape­worm pro­tein on its own. This indic­ates that the res­ist­ant pop­u­la­tion was able to recog­nize a tape­worm infec­tion and ini­ti­ate fibrosis, while the oth­er pop­u­la­tions could not. We also found that the res­ist­ant pop­u­la­tion was able to start pro­du­cing fibrosis much faster than the oth­er pop­u­la­tions, with­in 24 hours after the injec­tion. Evol­u­tion has likely favored this fast reac­tion so that these fish can con­trol and kill tape­worms while they are small. Towards the end of our exper­i­ment, we also dis­covered that the res­ist­ant pop­u­la­tion was able to start clear­ing their fibrosis, while the oth­er pop­u­la­tions con­tin­ued to have lots of fibrosis from the alum treat­ments, even up to 90 days after the injec­tion. Oth­er stud­ies have found that fibrosis can be costly for stickle­back, decreas­ing their abil­ity to swim and repro­duce. To help avoid these costs, res­ist­ant fish appear to have evolved the abil­ity to resolve fibrosis after clear­ing a tape­worm infection.

So, at what step does para­site res­ist­ance evolve? Accord­ing to our res­ults, the crit­ic­al point for our stickle­back pop­u­la­tions is when fish first detect the para­site and ini­ti­ation their response. Our study also demon­strates that suc­cess or fail­ure at each step in the host response influ­ences wheth­er evol­u­tion will be able to act on the fol­low­ing steps. Because res­ist­ant fish can recog­nize and respond to tape­worms, they have evolved to respond rap­idly, while tape­worms are small, and resolve that response once the danger has passed. By exper­i­ment­ally isol­at­ing dif­fer­ent stages of the host response to infec­tion, we were able to dis­cov­er where key dif­fer­ences lie between res­ist­ant and sus­cept­ible populations.

Dr Aman­da Hund is a James S McDon­nell Found­a­tion Postdoc­tor­al Fel­low at the Uni­ver­sity of Min­nesota. The ori­gin­al art­icle is freely avail­able to read and down­load from Evol­u­tion Letters.