Modeling the contribution of antibodies to the within-host dynamics of single and dual helminth infections in a natural system

Within-host models of infection can provide important insights into the processes that affect parasite spread and persistence in host populations. However, modeling is often limited by the availability of empirical data, a problem commonly encountered in natural systems. Here, we used six years of immune-infection observations of two gastrointestinal helminths (Trichostrongylus retortaeformis and Graphidium strigosum) from a population of European rabbits (Oryctolagus cuniculus) to develop an age-dependent, within-host mathematical model that explicitly included species-specific and cross-reacting antibody (IgA and IgG) responses to each helminth in hosts with single or dual infections. Different models of single infection were formally compared to test alternative mechanisms of parasite regulation. The two models that best described single infections of each helminth species were then coupled through antibody cross-immunity to examine how the presence of one species could alter the host immune response to, and the within-host dynamics of, the other species. For both single infections, model selection suggested that either IgA or IgG responses could equally explain the observed parasite intensities at different host age. However, the strength of this response drastically changed between the two helminths, being stronger against T. retortaeformis than against G. strigosum and causing contrasting age-intensity profiles. When the two helminths coinfect the same host, we found a decrease of the species-specific immune response to both species together with an asymmetric cross-immune response driven by IgG. Changes in the level and affinity of antibodies from single to dual infections contributed to the significant increase of both helminth abundances. By combining mathematical modeling with immuno-infection data, our work provides a model framework for disentangling some of the complexities generated by host-parasite and parasite-parasite interactions from natural systems. Our approach thus offers a tractable general tool to examine immune-infection relationships within hosts. Author summaryThe host immune response often plays a critical role in regulating parasite dynamics and transmission. We developed a mathematical model to evaluate whether and how the observed variation in host antibody responses could explain the relative differences in the abundance of two parasite species in hosts with single and dual infections from a natural rabbit population. Our results indicated that either IgA or IgG could describe the contrasting trends of the two parasites in rabbits with single infections. Specifically, antibodies appeared to control T. retortaeformis, while the effect was less clear for G. strigosum. For dual infections, we found a weaker specific antibody response against both helminths and an asymmetric cross-immunity, which could explain the significantly greater intensities observed for T. retortaeformis and, secondly, for G. strigosum. Our within-host mathematical framework provides a plausible mechanism for the mediated role of antibodies in hosts with single and dual parasite infections, and how the strength of these infection-immune interactions changes with host age. This model framework offers a way forward to our understanding of the within-host processes that generate individual variation in infection and is relatively flexible to be applied to other natural systems.