Recent evolution of extreme cestode growth suppression by a vertebrate host

Abstract

Parasites can be a major cause of natural selection on hosts, which consequently evolve a variety of strategies to avoid, eliminate, or tolerate infection. When ecologically similar host populations present disparate infection loads, this natural variation can reveal immunological strategies underlying adaptation to infection and population divergence. For instance, the tapeworm Schistocephalus solidus persistently infects between 0% to 80% of threespine stickleback (Gasterosteus aculeatus) in lakes on Vancouver Island. To test whether these heterogeneous infection rates are due to evolved differences in immunity, we experimentally exposed lab-reared fish from high-and low-infection populations, which are not known to differ in natural exposure risk, to controlled doses of Schistocephalus. We observed heritable between-population differences in several immune traits: fish from the naturally uninfected population initiated a stronger granulocyte response to Schistocephalus infection, and their granulocytes constitutively generated threefold more reactive oxygen species (ROS). Despite these immunological differences, Schistocephalus was equally successful at establishing initial infections in both host populations. However, the low-infection fish dramatically suppressed tapeworm growth relative to high-infection fish, and parasite size was intermediate in F1hybrid hosts. Our results show that stickleback recently evolved heritable variation in their capacity to suppress helminth growth. Comparative data from many from natural populations indicate that growth suppression is widespread but not universal and, when present, is associated with reduced infection prevalence. Host suppression of helminth somatic growth may be an important immune strategy that aids in parasite clearance, or in mitigating the fitness costs of persistent infection.Significance: Large parasites remain a persistent source of morbidity and mortality in humans, domesticated animals, and wildlife. Hosts are subject to strong natural selection to eliminate or tolerate these parasite infections. Here, we document the recent evolution of a striking form of resistance by a vertebrate host (threespine stickleback) against its cestode parasite (Schistocephalus solidus). After Pleistocene glacial retreat, marine stickleback colonized freshwater lakes, encountered Schistocephalus, and evolved varying levels of resistance to it. We show that a heavily-and a rarely-infected population of stickleback have similar resistance to Schistocephalus colonization, but rarely-infected fish suppress parasite growth by orders of magnitude. These populations represent ends of a natural continuum of cestode growth suppression, which is associated with reduced infection prevalence.

Male and female reproductive fitness costs of an immune response in natural populations

“…Cestode prevalence varies widely across lakes in Western Canada (Stutz et al 2014, Weber et al 2017b, and some stickleback populations do not exhibit fibrotic response to cestode infection (Weber et al in prep, Hund et al 2020). Our results indicate that variation in the costs and benefits of fibrosis across populations could explain this variation in stickleback immune response.…”

“…We captured adult threespine stickleback from two lakes (Boot Lake and Roselle Lake), on Vancouver Island, British Columbia, Canada, between June 2-8 2019. These lakes were chosen because Schistocephalus infection and fibrosis response are observed in both, although to substantially different degrees; fish in Roselle exhibit a strong fibrotic immune response yet relatively low cestode infection rates, while fish in Boot exhibit much higher infection rates and lower rates of fibrosis (Stutz et al 2014, Weber et al 2017b, Hund et al 2020). As noted above, the presence of both fibrosis and infection, imperfectly correlated, allows us to statistically partition their effects on measures of male and female reproductive success.…”

“…In addition to aiding host mortality, Schistocephalus infection is associated with reduced fecundity in females (Heins et al 2010). Presumably to mitigate such fitness costs, some stickleback populations have evolved resistance to Schistocephalus infection, although other populations remain susceptible (Scharsack et al 2007, Scharsack et al 2016, Weber et al 2017a, Weber et al 2017b. In particular, fish in some populations develop peritoneal fibrosis in response to cestode infection, in which their body cavity and organs become engulfed in scar-like connective tissue (Weber et al in prep) similar to human fibrotic response during tissue repair (Mutsaers et al 1997).…”

Phylogenetically conserved peritoneal fibrosis response to an immunologic adjuvant in ray-finned fishes

“…Our study was motivated by inter-population variation in threespine sticklebacks' ability to encapsulate parasitic tapeworm S. solidus (Weber et al 2017b). The inter-population variation probably stems from an evolutionary trade-off between the benefit of resistance (early encapsulation of the worm) and the risk of organ adhesion, excessive fibroblast proliferation, and ultimately partial sterility in the stickleback (Weber et al, in preparation; De Lisle and Bolnick, in preparation).…”

“…The threespine stickleback is the obligate intermediate host of this specialized parasite. Some populations of stickleback have evolved a capacity to suppress S. solidus growth by encapsulating it in fibrotic tissue, sometimes leading to successfully killing and eliminating the parasite (Weber et al 2017b).…”