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

Abstract

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.

Ecology, evolution and spillover of coronaviruses from bats

“…Co-infections with multiple pathogens can influence transmission to conspecifics and to spillover hosts. Cross-protective immunity from infection by related pathogens might reduce susceptibility or transmission, whereas trade-offs in immune response to one pathogen might increase susceptibility and facilitate transmission of another 39 , 51 . Co-infection of bats with multiple coronaviruses at the same time, or co-circulation of multiple virus genotypes within a roost, might result in interactions that affect the timing, location and intensity of virus shedding, as has been described in other viral families 39 .…”

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

“…Second, IgA is an important contributor to the regulation of helminth abundance and vital rates [40][41][42][43][44][45], where the degree of protection is strongly affected by the host-helminth system and its history of infection [46][47][48]. In this system, we found that IgA (but not IgG) follows the dynamics of the two helminths, suggesting a rapid response and a reasonable representation of the immune response that does exhibit some regulatory proprieties but no long-term protection [23][24][25][26][27]. Third and most important, we needed a variable with an antigenic-specific immune response that could allow the quantification of separate reactions, namely species-specific and cross-reacting signals and, as such, would capture the essence of symmetric/asymmetric interactions, while avoiding additional complexities of adding extra variables and unnecessary assumptions.…”

“…The dynamics of the two helminths could also be negatively affected by ecological processes of intra-specific competition for resources. Previous studies indicated that this is probably not the main mechanism of regulation for T. retortaeformis but could play a role for G. strigosum, especially at high abundances [26,31]. For example, rabbits nutritionally constrained, through coprophagic restriction and on a fixed diet, carried the same T. retortaeformis intensities as animals on a fixed diet only [32].…”

“…Laboratory experiments showed that rabbits develop a type 2 anti-inflammatory response against both species. However, while this regulates both T. retortaeformis intensity and body growth, which then affects fecundity, it appears to have a weaker effect against G. strigosum that maintains high intensities throughout the infection [24][25][26][27]. A broader investigation of the immune profile in experiments of infection and anthelminthic treatment found a down-regulation of genes expressing type 1, type 2 and T-regulatory responses during reinfections with G. strigosum and much less so with T. retortaeformis, both in single and dual infections [23].…”

“…We used two helminth species, Trichostrongylus retortaeformis and Graphidium strigosum, that inhabit different gastrointestinal niches of the European rabbit (Oryctolagus cuniculus), the small intestine and stomach respectively, implying that they were unlikely to exhibit direct competition. While both helminths cause chronic infections, T. retortaeformis, and less so G. strigosum, shows evidence of regulation of abundance and fecundity through host immunity [22][23][24][25][26][27]. Interestingly, field studies found higher intensities of the first and to a lesser extent the second in rabbits with both helminths, when compared to hosts with single infections [28,29], suggesting a possible positive interaction between the two species.…”