Lessons in Mind Control: Trends in Research on the Molecular Mechanisms behind Parasite-Host Behavioral Manipulation

Abstract

Scientific and public interest in host manipulation by parasites has surged over the past few decades, resulting in an exponential growth of cases where potential behavioral manipulation has been identified. However, these studies dwarf the number of genuine attempts to elucidate the mechanistic processes behind this behavioral manipulation. Ultimately, this imbalance has slowed progress in the study of the mechanisms underlying host manipulation. As it stands, research suggests that the mechanisms of host manipulation fall into three categories: immunological, genomic/proteomic and neuropharmacological, and forth potential category: symbioant-mediated manipulation. After exploration of the literature pertaining to these four pathways, four major trends become evident. First and foremost, there is a severe disconnect between the observed molecular and behavioral shifts in a parasitized host. Indeed, very rarely a study demonstrates that molecular changes observed in a host are the result of active manipulation by the resident parasite, or that these molecular changes directly result in behavioral manipulation that increases the parasite's fitness. Secondly, parasites may often employ multiple pathways in unison to achieve control over their hosts. Despite this, current scientific approaches usually focus on each manipulation pathway in isolation rather than integrating them. Thirdly, the relative amount of host-parasite systems yet to be investigated in terms of molecular manipulation is staggering. Finally, as a result of the aforementioned trends, guiding mechanisms or principles for the multiple types of behavioral manipulation are yet to be found. Researchers should look to identify the manipulative factors required to generate the molecular changes seen in hosts, while also considering the "multi-pronged" approach parasites are taking to manipulate behavior. Assessing gene expression and its products during transitional periods in parasites may be a key methodological approach for tackling these recent trends in the host manipulation literature.

Survival of the feces: Does a nematode lungworm adaptively manipulate the behavior of its cane toad host?

“…The same holds true for other behavioral differences we observed between infected and uninfected hosts; the impact of behaviors on lifetime fitness of the parasite (and host) must be established to provide compelling evidence that manipulation is occurring (Cézilly & Perrot‐Minnot, ; Perrot‐Minnot et al., ). Identifying the mechanisms by which parasites manipulate their hosts remains a formidable challenge, but advances in gene expression techniques hold promise in this respect (Feldmeyer et al., ; Herbison, ).…”

Invisible Designers: Brain Evolution Through the Lens of Parasite Manipulation

“…Unsurprisingly, then, parasites have evolved a striking variety of biochemical means of manipulation. For ease of presentation, these mechanisms can be grouped into three overlapping categories: immunological, neuropharmacological, and genomic/proteomic (Adamo 2013;Herbison 2017).…”

“…Since the immune system is designed to detect and react to parasites and to modulate a range of neural and behavioral processes in the host, one could say that immune pathways are preadapted for ma-nipulation (Adamo 2013). At the same time, immune reactions normally function to benefit the host; this makes it hard to conclusively demonstrate that a given behavioral symptom is in the interest of the parasite (Herbison 2017). Most of the putative examples come from invertebrates.…”

“…In gammarids infected by various species of helminths, the changes in serotonergic transmission induced by the parasites (see below) seem to be partly mediated by neuroinflammation, through the release of cytokines and nitric oxide (Helluy 2013). Abundant cytokines and nitric oxide are also released when toxoplasma cysts infect the brain of the host; but as in most other vertebrate examples, it is unclear whether the immune reactions triggered by the parasite are part of an adaptive manipulation strategy (see Herbison 2017).…”

“…Research on behavioral manipulation has focused almost exclusively on the evolution of parasites and their strategies. This includes the specific biochemical mechanisms employed by parasites (e.g., Adamo 2012Adamo , 2013Perrot-Minnot and Cézilly 2013;Herbison 2017;Libersat et al 2018), the evolutionary trajectories that lead to manipulation (e.g., Poulin 2010; Thomas et al 2012;Loreto et al 2018), and the corresponding tradeoffs (e.g., Poulin et al 2005;Roitberg 2012). What has been almost entirely neglected is the effect of parasites on the evolution of their hosts' nervous and endocrine systems.…”