Modulation of the immune response by helminths: a role for serotonin?

Abstract

The mammalian gut is a remarkable organ: with a nervous system that rivals the spinal cord, it is the body’s largest repository of immune and endocrine cells and houses an immense and complex microbiota. Infection with helminth parasites elicits a conserved program of effector and regulatory immune responses to eradicate the worm, limit tissue damage, and return the gut to homeostasis. Discrete changes in the nervous system, and to a lesser extent the enteroendocrine system, occur following helminth infection but the importance of these adaptations in expelling the worm is poorly understood. Approximately 90% of the body’s serotonin (5-hydroxytryptamine (5-HT)) is made in enterochromaffin (EC) cells in the gut, indicative of the importance of this amine in intestinal function. Signaling via a plethora of receptor subtypes, substantial evidence illustrates that 5-HT affects immunity. A small number of studies document changes in 5-HT levels following infection with helminth parasites, but these have not been complemented by an understanding of the role of 5-HT in the host–parasite interaction. In reviewing this area, the gap in knowledge of how changes in the enteric serotonergic system affects the outcome of infection with intestinal helminths is apparent. We present this as a call-to-action by investigators in the field. We contend that neuronal EC cell–immune interactions in the gut are essential in maintaining homeostasis and, when perturbed, contribute to pathophysiology. The full affect of infection with helminth parasites needs to define, and then mechanistically dissect the role of the enteric nervous and enteroendocrine systems of the gut.

The impact of Anguillicoloides crassus (Nematoda) on European eel swimbladder: histopathology and relationship between neuroendocrine and immune cells

“…In contrast, no endocrine cells positive to the above antibodies were observed in the epithelium of swimbladders with very few adults and with no larvae in the lumen. About 90% of the body's 5-HT is produced by enterochromaffin cells in the gut, which reveals the importance of this amine in gut function (Wang et al ., 2018). Lundin and Holmgren (1989) reported the expression of 5-HT in the swimbladder epithelial cells of four fish species.…”

“…Lundin and Holmgren (1989) reported the expression of 5-HT in the swimbladder epithelial cells of four fish species. Serotonin is one of the most important mediator molecules in inflammation caused by helminths (Dezfuli et al ., 2000, 2002; Bosi et al ., 2005 a ; Wang et al ., 2018). Recently, Gonzáles-Stegmaier et al .…”

“…(2017) have demonstrated the pro-inflammatory effects of NPY in the SHK-1 cell line and head kidney of the Atlantic salmon Salmo salar . In heavily infected swimbladder of eels, the occurrence of numerous positive cells to anti-NPY and -5-HT antibodies might suggest their involvement in inflammatory response against helminths, as they are active in immune cells recruitment and host local defence (Bosi et al ., 2005 a ; Gonzáles-Stegmaier et al ., 2017; Dezfuli et al ., 2018; Wang et al ., 2018).…”

Histopathological changes induced by the digenean intestinal parasite Masenia nkomatiensis Dumbo, Dos Santos, & Avenant‐Oldewage, 2019 of the catfish Clarias gariepinus (Burchell) from Incomati Basin, Mozambique

“…Accumulation of these cells in the site of infection has been thoroughly documented for digeneans and cestodes (Dezfuli et al, , , ; El‐Mansy & Hamada, ). Another type of phagocytic granulocyte, the neutrophil, is a rapid responder following infection and tissue damage (Wang et al, ). However, its low number in parasitized hosts, as found in this study, may indicate a tendency of losing innate defence mechanism in chronic infections due to the lysis of these cells by the enzymes of the parasite (Parvathi & Karemungikar, ).…”

“…Infection with a helminth parasite is a potent stimulus for host immunity that seeks to inactivate and eradicate the worm, whereas the parasite strives to circumvent the host's anti-worm efforts, allowing establishment, access to nutrients and completion of its life cycle (Wang, Sharkey, & McKay, 2018). This intimate relationship generally exposes the host to antigenic substances of parasite origin (Bogitsh, Carter, & Oeltmann, 2012).…”