The missing link in parasite manipulation of host behaviour

Abstract

The observation that certain species of parasite my adaptively manipulate its host behaviour is a fascinating phenomenon. As a result, the recently established field of ‘host manipulation’ has seen rapid expansion over the past few decades with public and scientific interest steadily increasing. However, progress appears to falter when researchers ask how parasites manipulate behaviour, rather than why. A vast majority of the published literature investigating the mechanistic basis underlying behavioural manipulation fails to connect the establishment of the parasite with the reported physiological changes in its host. This has left researchers unable to empirically distinguish/identify adaptive physiological changes enforced by the parasites from pathological side effects of infection, resulting in scientists relying on narratives to explain results, rather than empirical evidence. By contrasting correlative mechanistic evidence for host manipulation against rare cases of causative evidence and drawing from the advanced understanding of physiological systems from other disciplines it is clear we are often skipping over a crucial step in host-manipulation: the production, potential storage, and release of molecules (manipulation factors) that must create the observed physiological changes in hosts if they are adaptive. Identifying these manipulation factors, via associating gene expression shifts in the parasite with behavioural changes in the host and following their effects will provide researchers with a bottom-up approach to unraveling the mechanisms of behavioural manipulation and by extension behaviour itself.

The secretome of a parasite alters its host’s behaviour but does not recapitulate the behavioural response to infection

“…To demonstrate that behavioural changes in the host are the result of direct parasitic manipulation, it is crucial to find the manipulation factors produced by the parasite and their source, and to test how they impact the physiology and behaviour of the host. Such a link has almost never been established in previous studies of parasitic manipulation (9). Parasites release a wide variety of molecules into their external environment, including lipids (10), nucleic acids (11) and proteins (12), which are sometimes included in extracellular vesicles (13).…”

“…For example, ants infected by the fungus Ophiocordyceps leave their normal activities and climb into the vegetation, which facilitates the propagation of the parasite’s spores (6). If parasites are manipulative, they should disturb the functioning of their host central nervous system and physiological systems (hormonal and immune systems) by the production, storage, and release of molecules called manipulation factors (7–9). To demonstrate that behavioural changes in the host are the result of direct parasitic manipulation, it is crucial to find the manipulation factors produced by the parasite and their source, and to test how they impact the physiology and behaviour of the host.…”

The contrasting hidden consequences of parasitism: Effects of a hematophagous nematode (Uncinaria sp.) in the development of a marine mammal swimming behavior

“…Hookworm infection also alters the social behavior of pups, since hookworm‐infected pups on land decreased their level of social activity and they were less likely to be observed playing in water, a behavior associated with the formation of “spots” or social groups. Increases or decreases in social behavior due to parasitism are well documented in several taxa, but the mechanisms that drive these changes are not well understood (Ezenwa et al, ; Herbison, Lagrue, & Poulin, ). In this system, we predicted that social behavior could be decreased due to the detrimental effects of hookworms in energy balance and hemoglobin levels, which could restrain the movement of sick pups.…”

Hypothesized behavioral host manipulation by SARS-CoV2/COVID-19 infection

“…Survival is the most critical goal for different pathogens and parasites, especially concerning their chances of reproduction. Past research has shown that behavioral host manipulation can occur to promote the best interest of the pathogen [1,2]. Host manipulation can be viewed as adaptations that commandeer the behavior and actions of the host in ways that promote the reproductive best interests of the virus.…”

“…Benefits may result in increased chances of transmission and survival. Host manipulation has been recognized in a number of pathogens such as toxoplasmosis, rabies, and influenza [1,2,3,4,5,6]. It is important to mention that certain pathogens are neuro-invasive, and understanding how it targets and manipulates the central nervous system (CNS) can broaden possible questions about host manipulation [7,8].…”