Parasite-induced alterations of sensorimotor pathways in gammarids: collateral damage of neuroinflammation?

Some larval helminths alter the behavior of their intermediate hosts in ways that favor the predation of infected hosts, thus enhancing trophic transmission. Gammarids (Crustacea: Amphipoda) offer unique advantages for the study of the proximate factors mediating parasite-induced behavioral changes. Indeed, amphipods infected by distantly related worms (acanthocephalans, cestodes and trematodes) encysted in different microhabitats within their hosts (hemocoel, brain) present comparable, chronic, behavioral pathologies. In order to evaluate the potential connection between behavioral disturbances and immune responses in parasitized gammarids, this Review surveys the literature bearing on sensorimotor pathway dysfunctions in infected hosts, on the involvement of the neuromodulator serotonin in altered responses to environmental stimuli, and on systemic and neural innate immunity in arthropods. Hemocyte concentration and phenoloxidase activity associated with melanotic encapsulation are depressed in acanthocephalan-manipulated gammarids. However, other components of the arsenal deployed by crustaceans against pathogens have not yet been investigated in helminth-infected gammarids. Members of the Toll family of receptors, cytokines such as tumor necrosis factors (TNFs), and the free radical nitric oxide are all implicated in neuroimmune responses in crustaceans. Across animal phyla, these molecules and their neuroinflammatory signaling pathways are touted for their dual beneficial and deleterious properties. Thus, it is argued that neuroinflammation might mediate the biochemical events upstream of the serotonergic dysfunction observed in manipulated gammarids - a parsimonious hypothesis that could explain the common behavioral pathology induced by distantly related parasites, both hemocoelian and cerebral.

Parasitic manipulation and neuroinflammation: Evidence from the system Microphallus papillorobustus (Trematoda) - Gammarus (Crustacea).

BACKGROUND: Neuropathological consequences of neuroinflammatory processes have been implicated in a wide range of diseases affecting the central nervous system (CNS). Glial cells, the resident immune cells of the CNS, respond to tissue injury by releasing proinflammatory cytokines and free radicals such as nitric oxide. We explored the possibility that neuroimmune responses are involved in parasitic manipulation of host behavior in a trematode-crustacean association. The cerebral larva of the flatworm Microphallus papillorobustus alters responses to environmental stimuli - and thus reflex pathways - in the crustacean Gammarus insensibilis, in a way that enhances predation of the crustacean by birds, definitive hosts of the parasite. RESULTS: Immunocytochemical experiments followed by confocal microscopy were performed to study the distribution of glutamine synthetase, a glial cell marker, and nitric oxide synthase in the brain of gammarids. Astrocyte-like glia and their processes were abundant at the surface of the parasites while levels of nitric oxide synthase were elevated at the host-parasite interface in the brain of gammarids harboring mature cerebral larvae and demonstrating altered behavior. CONCLUSION: Taken together these results lend support to the neuroinflammation hypothesis whereby a chronic CNS specific immune response induced by the parasite plays a role in the disruption of neuromodulation, neuronal integrity, and behavior in infected hosts.