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.

Keywords: Behaviour; Manipulation; Manipulation factor; Mechanism; Parasite.

Fig. 1

Hypothetical host-parasite system where parasite establishment in the host coincides with Alpha-1 (neurochemical/hormone) upregulation in the central nervous system (CNS) of the host. Arrows demonstrate multiple potential explanations for alpha-1 upregulation. Green arrows: Parasite may directly impact Alpha-1 regulation resulting in adaptive behavioural manipulation, but it may also trigger homeostatic and/or immunological mechanisms of the host. Alpha-1 upregulation could also be a by-product of the real mechanism for manipulation or an immune evasion strategy by the parasite. Orange arrows: Parasite establishment may stimulate immunological defense mechanisms which require the upregulation of Alpha-1, or conversely increased Alpha-1 presence may be a side effect of immunlogical activation from parasite establishment. Red arrows: Parasite establishment may trigger mechanisms involving alpha-1 designed to maintain homeostasis. By extension, Alpha-1 could be primarily involved in inducing sickness behaviours designed to return the host to homeostasis

Fig. 2

Hypothetical host-parasite system where the parasite is adaptively manipulating behaviour via Alpha-1 upregulation in the central nervous system (CNS) of the host. The major known (1, 4, 5) and hypothetical (2, 3) steps required for adaptive behavioural manipulation are presented here. Evidence of steps 2 and 3 has allowed researchers to eliminate the possibility that Alpha-1 upregulation was a side effect of infection. Key: Numbers represent the known and potential fundamental steps in host manipulation: (1) Establishment of parasite in host (location of parasite will vary depending of host-parasite system i.e. CNS, muscle, digestive tract); (2) Source (potentially multiple different sources) of manipulation factors activates at a given time during the parasite's development cycle, releasing manipulation factors into the host; (3) Manipulation factors exert their effects on one or more physiological systems; (4) Molecular change in the host (i.e. Alpha-1 upregulation as in the hypothetical case of Fig. 1) as a result on manipulation factors released by the parasite; (5) Host behavior changes as a result of the molecular change induced by the manipulation factors. Behavioural alteration directly increases the parasite's fitness. Glossary: Manipulative factor: Any molecule/substance released by the parasite that alters the normal functioning of one or more of the major identified pathways for host manipulation, resulting in a molecular shift in the host which ultimately changes the host behavior for the benefit of the parasite; Manipulative factor source: A structure (organelle, membrane, gland, enzyme etc.) which generates manipulative factors for the parasite to use in host manipulation