Signaling in Parasitic Nematodes: Physicochemical Communication Between Host and Parasite and Endogenous Molecular Transduction Pathways Governing Worm Development and Survival

Abstract

Signaling or communication between host and parasite may occur over relatively long ranges to enable host finding and acquisition by infective parasitic nematode larvae. Innate behaviors in infective larvae transmitted from the soil that enhance the likelihood of host contact, such as negative geotaxis and hypermotility, are likely mediated by mechanoreception and neuromuscular signaling. Host cues such as vibration of the substratum, elevated temperature, exhaled CO2, and other volatile odorants are perceived by mechanosensory and chemosensory neurons of the amphidial complex. Beyond this, the molecular systems that transduce these external cues within the worm are unknown at this time. Overall, the signal transduction mechanisms that regulate switching between dauer and continuous reproductive development in Caenorhabditis elegans, and doubtless other free-living nematodes, have provided a useful framework for testing hypotheses about how the morphogenesis and development of infective parasitic nematode larvae and the lifespan of adult parasites are regulated. In C. elegans, four major signal transduction pathways, G protein-coupled receptor signaling, insulin/insulin-like growth factor signaling, TGFβ-like signaling and steroid-nuclear hormone receptor signaling govern the switch between dauer and continuous development and regulate adult lifespan. Parasitic nematodes appear to have conserved the functions of G-protein-coupled signaling, insulin-like signaling and steroid-nuclear hormone receptor signaling to regulate larval development before and during the infective process. By contrast, TGFβ-like signaling appears to have been adapted for some other function, perhaps modulation of the host immune response. Of the three signal transduction pathways that appear to regulate development in parasitic nematodes, steroid-nuclear hormone signaling is the most straightforward to manipulate with administered small molecules and may form the basis of new chemotherapeutic strategies. Signaling between parasites and their hosts’ immune systems also occurs and serves to modulate these responses to allow chronic infection and down regulate acute inflammatory responses. Knowledge of the precise nature of this signaling may form the basis of immunological interventions to protect against parasitism or related lesions and to alleviate inflammatory diseases of various etiologies.

Comparative morphology and biology of nematodes of genus Heterakis (Nematoda, Heterakidae), parasites of the domestic goose (Anser anser) in Ukraine

“…Their expected diversity may well equal a million species, and most known species can parasitize in humans, animals and plants (Blaxter et al, 1998;Castagnone-Sereno & Danchin, 2014). Parasitic nematodes are essential components of biocoenoses; they utilize a lot of energy in ecosystems and can regulate the abundance of their hosts (Bongers & Ferris, 1999;Lok, 2016;Viney, 2017). Nematodes are the most widely distributed parasites of domestic and wild animals, and the genus Heterakis Dujardin, 1845 includes especially common and prevalent parasite species.…”

Advances in the Molecular and Cellular Biology of Strongyloides spp.

“…For over two decades, the morphological, behavioral, and molecular genetic aspects of dauer larval development in C. elegans have been regarded as a paradigm for framing hypothesis about the molecular signaling mechanisms that govern the development of iL3 of parasitic nematodes before, during, and after the infective process [75]. Published findings support that the canonical dauer regulatory signaling pathways in C. elegans, G protein-coupled sensory signaling, insulin-like signaling and steroid-nuclear receptor (NR) signaling involving homologs of the DAF-12 NR, and its dafachronic acid ligands are conserved in several soiltransmitted parasitic nematode species, including Strongyloides spp., and operate in sequence to regulate developmental arrest of iL3 in the environment and their reactivation following host infection [76]. The DAF-12 NR is conserved in S. stercoralis and Ancylostoma caninum, and developing larvae of these parasites respond to exogenous dafachronic acids in a manner consistent with dauer hypothesis [77].…”

Developmental Regulation of Dirofilaria Immitis Microfilariae and Evaluation of Ecdysone Signaling Pathway Transcript Level Using Droplet Digital Polymerase Chain Reaction

“…EcR, rxr-1 and downstream early regulatory genes are upregulated in developing micro lariae As the steroid-nuclear hormone receptor signaling plays an important role in ecdysozoans development [44], micro lariae were collected every 3 days and the transcript levels of the DimEcR, Dim-rxr-1, and downstream early regulatory genes were measured to determine the transcriptional change in the ecdysteroid signaling pathway during micro larial developmental changes. Dimnhr-7 and Dim-nhr-6, orthologues of E78 and E75, respectively, are both downstream early regulatory genes of the ecdysone receptor.…”