Quantitative assessment of spicule length in Heligmosomoides spp. (Nematoda, Heligmosomidae): distinction between H. bakeri, H. polygyrus and H. glareoli.

Nematode spicules play a vital role in the reproductive activity of species that possess them. Our primary objective was to compare the lengths of spicules of the laboratory mouse (Mus musculus) ­ maintained isolate H. bakeri ­ with those of H. polygyrus from naturally infected wood mice (Apodemus sylvaticus). On a more limited scale, we also included H. glareoli from bank voles (Myodes glareolus), a species reputed to possess longer spicules than either of the 2 former species. In total, we measured 1264 spicules (H. bakeri, n = 614; H. polygyrus n = 582; and H. glareoli, n = 68). There was a highly significant difference between the spicule lengths of the Nottingham-maintained H. bakeri (mean = 0.518 mm) and H. polygyrus (0.598 mm) from 11 different localities across the British Isles. A comparison of the spicules of H. bakeri maintained in 4 different laboratories in 3 continents revealed a range in the mean values from 0.518 to 0.540 mm, while those of worms from Australian wild house mice were shorter (0.480 mm). Mean values for H. polygyrus from wood mice from the British Isles ranged from 0.564 to 0.635 mm, although isolates of this species from Norway had longer spicules (0.670 mm). In agreement with the literature, the spicules of H. glareoli were considerably longer (1.098 mm). Since spicules play a vital role in the reproduction of nematode species that possess them, the difference in spicule lengths between H. bakeri and H. polygyrus adds to the growing evidence that these 2 are quite distinct species and likely reproductively isolated.

A host-independent role for Fasciola hepatica transforming growth factor-like molecule in parasite development.

The trematode parasite Fasciola hepatica causes chronic infection in hosts, enabled by an immunosuppressed environment. Both host and parasite factors are known to contribute to this suggesting that avoidance of immunopathology is beneficial to both parties. We have previously characterised a parasite transforming growth factor (TGF)-like molecule, FhTLM, that interacts with host macrophages to prevent antibody-dependent cell cytotoxicity (ADCC). FhTLM is one of many described helminth TGF homologues and multiple helminths are now known to utilise host immune responses as developmental cues. To test whether, or how, F. hepatica uses FhTLM to manipulate host immunity, we initially examined its effects on the CD4 T-cell phenotype. Despite inducing IL-10, there was no induction of FoxP3 within the CD4 T-cell compartment. In addition to inducing IL-10, a wide range of chemokines were elicited from both CD4 T-cells and macrophages. However, no growth or survival advantage was conferred on F. hepatica in our co-culture system when CD4 T-cells, macrophages, or eosinophils were tested. Finally, using RNA interference we were able to verify a host-independent role for FhTLM in parasite growth. Despite the similarities of FhTLM with other described helminth TGF homologues, here we demonstrate species-specific divergence.

Evasion of Host Immunity During Fasciola hepatica Infection.

Fasciola hepatica, the common liver fluke, causes infection of livestock throughout temperate regions of the globe. This helminth parasite has an indirect lifecycle, relying on the presence of the mud snail to complete its transition from egg to definitive host (Beesley et al., Transbound Emerg Dis 65:199-216, 2017). Within the definitive host, the parasite excysts in the intestine forming a newly excysted juvenile (NEJ) and migrates via the peritoneal cavity to the liver. Disease resulting from infection can be acute or chronic depending on the host and the number of parasites present. Sheep may succumb to a fatal acute infection if the challenge of metacercariae is great enough. However, in cattle chronic disease is the most likely outcome with parasites surviving for long periods of time. Annual losses are estimated to be in the region of US$ 2000 million to the agricultural industry (Beesley et al., Transbound Emerg Dis 65:199-216, 2017). Management of the disease depends heavily on chemotherapy with triclabendazole being the drug of choice, consistent use for over 20 years has resulted in drug-resistant strains emerging worldwide (Beesley et al., Int J Parasitol 47:11-20, 2017). A more sustainable approach to control would be through vaccination and indeed a lead candidate has been identified, cathepsin L1. Despite these promising results the parasite continues to confound our own and host efforts to generate long-lasting and effective immunity. In this brief review we focus our attention on those mechanisms that the parasite utilises to circumvent the innate based defense mechanisms within the host.

Fasciola hepatica, TGF-ß and host mimicry: the enemy within.

Helminths parasites undergo developmental changes and migration within their definitive host, in addition to establishing chronic infection. Essential to this is the evasion of host immune responses; the canonical Th2 response is effective at removing parasites resident in the intestine. Conversely, helminths also promote the development of antigen-specific anergy and regulation. This often limits pathology but allows parasite survival, parasite effectors mediating this are the subject of intense study. They may be useful as future vaccine targets or xenogenic therapeutics. Fasciola hepatica possesses a family of TGF-like molecules of which one member, FhTLM, is capable of promoting intrinsic and extrinsic effects. Here we review the extrinsic effects of FhTLM on the host macrophage and its consequences for protective immunity. This review also discusses the specificities of FhTLM in light a very recent description of a nematode TGF-ß mimic and the effects of endogenous TGF-ß.