The Enemy of my Enemy is my Friend: Immune-Mediated Facilitation Contributes to Fitness of Co-Infecting Helminths

Abstract

Our conceptual understanding of immune-mediated interactions between parasites is rooted in the theory of community ecology. One of the limitations of this approach is that most of the theory and empirical evidence has focused on resource or immune-mediated parasite competition and yet, there is ample evidence of positive interactions between species that could be generated by immune-mediated facilitation. Here, we develop an immuno-epidemiological framework and apply it to longitudinal infection data of two gastrointestinal helminths that infect a population of free-living rabbits to investigate, through model testing, the mechanisms of immune-mediated facilitation in dual infections. Simulations show that weakened, species-specific IgA antibody responses and unequal, albeit low, IgA cross-reactions explain higher parasite intensities in dual compared to single infections, for both helminths. Simulations also show that rabbits with dual infections shed more free-living stages that survive fort longer in the environment, implying greater onward transmission than hosts with single infections. These findings support the hypothesis that the two helminths interact through immune-mediated facilitation which contributes to greater fitness and the long-term co-circulation of both species in the host population.

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

“…The down-modulation of the immune response by G. strigosum was also suggested as a possible mechanism that facilitated the accumulation of this helminth and, in turn, could have also contributed to the higher intensities of T. retortaeformis in co-infected rabbits, when compared to hosts with single infections (32). More recently, the modeling of these two helminths from this dataset (including the population of the current study) supported the role of IgA-mediated facilitation as a plausible mechanism that could explain the higher intensities of the two helminths in co-infected rabbits (46). A more complex model framework centered around the IL4-IgA immune interaction and data from laboratory experiments showed that, although the two helminths stimulated a similar immune response, changes in IgA and IL4 levels could describe the rapid clearance observed for T. retortaeformis but not G. strigosum when compared to single infections (48,50).…”

“…Therefore, we cannot exclude that some of the variations observed in the intensity of infection at specific age classes was affected by temporal changes in the exposure of rabbits to the pool of free-living stages. This issue and the role of climatic drivers in the availability of free-living stages is currently being investigated (46).…”

“…G. strigosum settles in the stomach while T. retortaeformis in the small intestine, where they then develop into adults, reproduce and shed eggs back onto the pasture through the rabbit’s feces (49,50). The two helminths are often found coinfecting the same rabbit (51,54) with intensities that vary differently with host age and seasonal trends (46,52,55).…”

“…G. strigosum settles in the stomach while T. retortaeformis in the small intestine, where they then develop into adults, reproduce and shed eggs back onto the pasture through the rabbit's feces (49,50). The two helminths are often found coinfecting the same rabbit (51,54) with intensities that vary differently with host age and seasonal trends (46,52,55). Previous studies from natural rabbit populations (51,52), including data used for the current work (54), showed that T. retortaeformis intensities peak in young rabbits and decrease in older hosts, while G. strigosum intensities accumulate with host age with weak or no evidence of parasite control.…”

“…These interspecific interactions have been modeled by borrowing again the predator-prey concept, where a single generalist predator, represented by host immunity, can target several preys represented by the community of coinfecting parasites (40)(41)(42). By mediating the interactions between parasite species, the immune response can contribute to processes of competition (36,43) or facilitation (44)(45)(46) within individual hosts, and in turn affect the transmission of the coinfecting species at the host population level. The study of the immunemediated mechanisms of interaction between helminths has strengthened our understanding of the dynamics of coinfection (47), however, the design and implementation of models contrasted to empirical data from field systems has been largely neglected.…”