The right response at the right time: Exploring helminth immune modulation in sticklebacks by experimental coinfection

Abstract

Parasites are one of the strongest selective agents in nature. They select for hosts that evolve counter‐adaptive strategies to cope with infection. Helminth parasites are special because they can modulate their hosts’ immune responses. This phenomenon is important in epidemiological contexts, where coinfections may be affected. How different types of hosts and helminths interact with each other is insufficiently investigated. We used the three‐spined stickleback (Gasterosteus aculeatus) – Schistocephalus solidus model to study mechanisms and temporal components of helminth immune modulation. Sticklebacks from two contrasting populations with either high resistance (HR) or low resistance (LR) against S. solidus, were individually exposed to S. solidus strains with characteristically high growth (HG) or low growth (LG) in G. aculeatus. We determined the susceptibility to another parasite, the eye fluke Diplostomum pseudospathaceum, and the expression of 23 key immune genes at three time points after S. solidus infection. D. pseudospathaceum infection rates and the gene expression responses depended on host and S. solidus type and changed over time. Whereas the effect of S. solidus type was not significant after three weeks, T regulatory responses and complement components were upregulated at later time points if hosts were infected with HG S. solidus. HR hosts showed a well orchestrated immune response, which was absent in LR hosts. Our results emphasize the role of regulatory T cells and the timing of specific immune responses during helminth infections. This study elucidates the importance to consider different coevolutionary trajectories and ecologies when studying host‐parasite interactions.

Cross-continental experimental infections reveal distinct defence mechanisms in populations of the three-spined stickleback Gasterosteus aculeatus

“…Neither parasite origin, nor sympatry had an effect on parasite size and the PI did not differ significantly between Alaskan populations. In line with previous results [ 31 , 46 ], quantitative resistance was much lower in DE stickleback, indicating a dominant host effect.…”

The host phenotype and microbiome varies with infection status, parasite origin and parasite microbiome composition

“…Our results indicate that the microbiome composition of fish exposed to S. solidus strongly depends on host genotype. In control individuals, we observed host genotype-specific constitutive differences in microbiome composition that confirm that host-based selective processes shape the organism microbiota [86][87][88], probably due to constitutive differences in immune gene expression pathways between populations [33,73,89,90]. In agreement, we found host-genotype dependent differences in the relationship between key immune genes and abundance of bacterial families, indicating that fish of different origins have developed different sensitivity to different bacterial families.…”

“…The observed limited parasite genotype effect on the microbiome of fish that resisted the parasite, together with the fact that the parasite has a very limited time to directly interact with gut microbes supports the hypothesis of a differential modulation of the immune response by different parasite genotypes that indirectly impact the host microbiome. Variations in the immune response the host mount during infection can either result from locally adapted parasites that differentially manipulate the host immune system [90,92], or from the host mounting a defense mechanism that differentiate between parasite genotypes [33,73,93,94]. In support of parasite local adaptation, we showed that parasites of different origin differentially impact the correlation between host microbiome composition and immune gene expression.…”

“…In fact, until now, studies comparing threespine stickleback immune gene expression and other immunological parameters could not reveal differences between control and exposed but non-infected sticklebacks [33,72]. However, we recently observed an impact of exposure on threespine stickleback hepatosomatic index and body condition, traditionally used as a measure of host condition [33,73]. This reduced host condition upon exposure suggests that the cost of resistance to infection, and elimination of the parasite through cell-mediated immunity within the first two weeks of infection [74] could indirectly impact the microbiome of exposed sticklebacks.…”

The application of community ecology theory to co‐infections in wildlife hosts

“…Therefore, for microparasites that internally replicate and are not easily cleared, longer time lags should allow the first parasite to reach higher densities in the host before a second parasite attempts to infect (Rojas et al 2005, Rosenblum et al 2012). Additionally, longer time lags and higher microparasite densities would allow for and cause elevated immune responses, respectively, increasing the likelihood that immunity alters co‐infection dynamics (Graham 2008, Piecyk et al 2019).…”