The interplay of helminthic neuropeptides and proteases in parasite survival and host immunomodulation

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.

Keywords: helminth; immunomodulation; neuropeptide.

Figure 1.

Phylogenetic tree of neuropeptides from different helminthic species such as C. elegans, Schistosoma sp, Ascaris sp, Schmidtea mediterranea, Macrostomum lignano (1A) and with Homo sapiens neuropeptides (1B). The Neighbor-joining trees was constructed using MEGA 5 software with 1000-fold bootstrap re-sampling. The numbers at the nodes of the branches represent the level of bootstrap support for each branch.

Figure 2.. Steps involved in the processing of neuropeptide from pre-pro-neuropeptide to a biologically active mature neuropeptide.

Figure 3.. Helminth-derived neuropeptides regulate the neuronal activity, promote Th2 immune responses and exert anti-microbial activity.