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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Comparative Immunology

Changes in gene regulation are associated with the evolution of resistance to a novel parasite

Provisionally accepted
Lauren  E FuessLauren E Fuess1,2*Amanda  K HundAmanda K Hund3Mariah  L KenneyMariah L Kenney2Meghan  F MaciejewskiMeghan F Maciejewski2,4Joseph  M MariniJoseph M Marini2Daniel  I BolnickDaniel I Bolnick2
  • 1Texas State University, San Marcos, United States
  • 2University of Connecticut, Storrs, United States
  • 3Carleton College, Northfield, United States
  • 4University of Illinois Urbana-Champaign, Urbana, United States

The final, formatted version of the article will be published soon.

Host-parasite interactions are ubiquitous and are important drivers of diversification and evolution. Host immune systems in particular are frequent targets of parasite-driven selection. The resulting rapid evolution of immune genes is usually framed as an ongoing ‘arms race’ between a co-evolving pair of host and parasite species. But, often immune evolution may be driven by the acquisition of a new and unfamiliar parasite. For instance, when marine populations of threespine stickleback (Gasterosteus aculeatus) colonized freshwater lakes ~12,000 years ago, they encountered a freshwater-restricted cestode Schistocephalus solidus, and evolved resistance. We compared the transcriptomic responses of lab-reared stickleback from three populations with varying cestode susceptibility, when exposed to several immune stimuli. The resulting changes in expression reveal strong evidence for shared and population-specific responses during evolution of defense against a new parasite. Our investigation highlights the roles of several key immunological processes in underlying a general physiological response to tissue damage (fibrosis), and the importance of regulation of this fibrosis as a necessary step for its co-option into defense against S.solidus tapeworms. Furthermore, we highlight changes in expression of fibrosis-associated genes which facilitate faster and more targeted deployment of this defense against parasites; fish from the most fibrosis-prone population exhibited constitutively higher expression of fibrosis-associated genes, but also stronger down-regulation of these genes after an initial stimulus from injected cestode proteins. Our results provide strong evidence that changes in gene regulation and increased negative feedback to mitigate immunopathology are essential steps in the evolutionary co-option of an existing pathway to defend against a new parasite.

Keywords: Ecoimmunology, evolutionary immunology, Fibrosis, host parasite, stickleback, Transcriptomics

Received: 01 Sep 2025; Accepted: 27 Jan 2026.

Copyright: © 2026 Fuess, Hund, Kenney, Maciejewski, Marini and Bolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Lauren E Fuess

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