Abstract
Neuropeptides comprise a diverse and broad group of neurotransmitters in vertebrates and invertebrates, with critical roles in neuronal signal transduction. While their role in controlling learning and memory in the brains of mammals is known, their extra-synaptic function in infection and inflammation with effects on distinct tissues and immune cells is increasingly recognized. Helminth infections especially of the central nervous system (CNS), such as neurocysticercosis, induce neuropeptide production by both host and helminth, but their role in host–parasite interplay or host inflammatory response is unclear. Here, we review the neurobiology of helminths, and discuss recent studies on neuropeptide synthesis and function in the helminth as well as the host CNS and immune system. Neuropeptides are summarized according to structure and function, and we discuss the complex enzyme processing for mature neuropeptides, focusing on helminth enzymes as potential targets for novel anthelminthics. We next describe known immunomodulatory effects of mammalian neuropeptides discovered from mouse infection models and draw functional parallels with helminth neuropeptides. Last, we discuss the anti-microbial properties of neuropeptides, and how they may be involved in host–microbiota changes in helminth infection. Overall, a better understanding of the biology of helminth neuropeptides, and whether they affect infection outcomes could provide diagnostic and therapeutic opportunities for helminth infections.
Highlights
Neurotransmitters are essential for neuronal signal transduction and are released by synaptic vesicles [1]
A mature neuropeptide is a short peptide of 3–100 amino acid residues, secreted by different types of cells to perform a variety of functions by binding to a diverse group of G-protein coupled receptors (GPCRs), leading to slow onset but long-lasting synaptic modulation [2,3]
T-cells express various neuropeptide receptors for substance P, calcitonin gene-related peptide (CGRP), somatostatin and vasoactive intestinal peptide (VIP), and direct interaction with respective neuropeptides of these receptors induces the release of IL-4, IL-10 and IL-2 cytokines [104,105]
Summary
Neurotransmitters are essential for neuronal signal transduction and are released by synaptic vesicles [1]. A mature neuropeptide is a short peptide of 3–100 amino acid residues, secreted by different types of cells (mostly of neuronal origin) to perform a variety of functions by binding to a diverse group of G-protein coupled receptors (GPCRs), leading to slow onset but long-lasting synaptic modulation [2,3]. Helminths are considered to have a very simple nervous system which is comprised mainly of neuronal cells and different types of nerve cords to transmit the signal molecules.
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