Within-host mechanisms of immune regulation explain the contrasting dynamics of two helminth species in both single and dual infections.

Variation in the intensity and duration of infections is often driven by variation in the network and strength of host immune responses. While many of the immune mechanisms and components are known for parasitic helminths, how these relationships change from single to multiple infections and impact helminth dynamics remains largely unclear. Here, we used laboratory data from a rabbit-helminth system and developed a within-host model of infection to investigate different scenarios of immune regulation in rabbits infected with one or two helminth species. Model selection suggests that the immunological pathways activated against Trichostrongylus retortaeformis and Graphidium strigosum are similar. However, differences in the strength of these immune signals lead to the contrasting dynamics of infections, where the first parasite is rapidly cleared and the latter persists with high intensities. In addition to the reactions identified in single infections, rabbits with both helminths also activate new pathways that asymmetrically affect the dynamics of the two species. These new signals alter the intensities but not the general trend of the infections. The type of interactions described can be expected in many other host-helminth systems. Our immune framework is flexible enough to capture different mechanisms and their complexity, and provides essential insights to the understanding of multi-helminth infections. Author summary: Hosts infected with parasites have developed complex immune strategies to regulate infection severity, however, these strategies are not always successful to confer long term protection. Here, we examine the immune reactions of hosts infected with one or two gastrointestinal parasites, using a rabbit-helminth system and a modeling approach to laboratory experiments. We found that similar immune interactions operate for the two parasites, however, changes in the strength of the relationships lead to contrasting dynamics of infections, where one parasite is quickly removed while the other shows no evidence of control. For hosts infected with both parasites we also found the activation of new immune reactions that asymmetrically affect the dynamics of the two parasites. While we observed changes in parasite intensity the general trends are conserved. Understanding how the immune reaction modulates host-parasite interactions can help to explain the often large variation in the host response to infections in natural systems. [ABSTRACT FROM AUTHOR]