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

Closely related populations often differ in resistance to a given
parasite, as measured by infection success or failure. Yet, the
immunological mechanisms of these evolved differences are rarely
specified. Does resistance evolve via changes to the host’s ability to
recognize that an infection exists, actuate an effective immune response,
or attenuate that response? We tested whether each of these phases of the
host response contributed to threespine sticklebacks’ recently evolved
resistance to their tapeworm Schistocephalus solidus. While marine
stickleback and some susceptible lake fish permit fast-growing tapeworms,
other lake populations are resistant and suppress tapeworm growth via a
fibrosis response. We subjected lab-raised fish from three populations
(susceptible marine ‘ancestors’, a susceptible lake population, a
resistant lake population), to a novel immune challenge using an injection
of: 1) a saline control, 2) alum, a generalized pro-inflammatory adjuvant
that causes fibrosis, 3) a tapeworm protein extract, or 4) a combination
of alum and tapeworm protein). With enough time, all three populations
generated a robust fibrosis response to the alum treatments. Yet, only the
resistant population exhibited a fibrosis response to the tapeworm protein
alone. Thus, these populations differed in their ability to respond to the
tapeworm protein but shared an intact fibrosis pathway. The resistant
population also initiated fibrosis faster in response to alum, and was
able to attenuate fibrosis, unlike the susceptible populations’ slow but
longer-lasting response to alum. As fibrosis has pathological side-effects
that reduce fecundity, the faster recovery by the resistant population may
reflect an adaptation to mitigate the costs of immunity. Broadly, our
results confirm that parasite detection and immune initiation, activation
speed, and immune attenuation simultaneously contribute to the evolution
of parasite resistance and adaptations to infection in natural
populations.