Within-host immune regulation and dynamics of helminth infection

The immune response developed against parasite infections often involves multiple mechanisms that change with the course and intensity of infection. These mechanisms can differ among parasite species and affect the severity and duration of an infection. When more than one parasite species is infecting the same host, the immune response is expected to change, both in term of strength of the reactions and components/processes involved, compared to single infections. Chiara Vanalli, a PhD student in the Cattadori lab, studied the within-host dynamics of infection of two species of gastrointestinal helminths in European rabbits using laboratory data and a modeling approach. Vanalli aimed to identify a parsimonious mechanism of immune regulation that could explain the different patterns of infection of the two helminths, and how these mechanisms changed in rabbits with single and dual infections. Understanding the mechanistic changes in the immune response from single to multiple infections, and the consequences for the intensity of infection, can provide useful knowledge on how heterogeneities to infection and transmission are generated.

     Parasitic helminths usually stimulate a type 2 immune reaction that involves cytokines, like IL4, and B-cell generated antibodies, such as IgA. In the presence of another infection, it’s expected that the immune mechanisms are fundamentally conserved but with a change in their magnitude and the activation or suppression of some immune components. Within-host mathematical models provide a key tool to disentangle some of these processes by offering a simplified mechanistic understanding of the host-parasite relationships. Vanalli tested different hypotheses of immune responses and their effect on the two helminth intensities. Focusing on the IL4-IgA processes, she found that the two helminths generated similar immunological pathways in single infections but differences in the strength of these immune signals led to the contrasting dynamics of infections, where T. retortaeformis was rapidly cleared from the small intestine and G. strigosum persisted with high intensities in the stomach. In addition to the reactions identified in single infections, rabbits with both helminths also activated new pathways that asymmetrically affected the dynamics of the two species by altering the intensities but not the general trend of the infections. Model selection suggested that the two helminths primarily interact via cross-stimulation, where the immune response to the first parasite species is also stimulated by the presence of the second species.

     The developed framework is flexible enough to capture different immune mechanisms and their complexity, providing essential insights to the understanding of multi-helminth infections and helping to explain the often large variation in the host response to infections in natural systems.

 

Synopsis written by: Chiara Vanalli