Huson, Kathryn M, Atcheson, Erwan, Oliver, Nicola AM, Best, Philip, Barley, Jason P, Hanna, Robert EB, McNeilly, Tom N, Fang, Yongxiang ORCID: 0000-0002-4514-5292, Haldenby, Sam, Paterson, Steve
ORCID: 0000-0002-1307-2981 et al (show 1 more authors)
(2021)
Transcriptome and Secretome Analysis of Intra-Mammalian Life-Stages of Calicophoron daubneyi Reveals Adaptation to a Unique Host Environment.
Molecular & cellular proteomics : MCP, 20.
100055-.
Abstract
Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock, which has seen a rapid rise in prevalence throughout Western Europe in recent years. After ingestion of metacercariae (parasite cysts) by the mammalian host, newly excysted juveniles (NEJs) emerge and invade the duodenal submucosa, which causes significant pathology in heavy infections. The immature flukes then migrate upward, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients, and avoid the host immune response. Here, transcriptome analysis of four intramammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic diseases, respectively), revealed how the expression and secretion of selected families of virulence factors and immunomodulators are regulated in accordance with fluke development and migration. Our data show that while a family of cathepsins B with varying S2 subsite residues (indicating distinct substrate specificities) is differentially secreted by NEJs and adult flukes, cathepsins L and F are secreted in low abundance by NEJs only. We found that C. daubneyi has an expanded family of aspartic peptidases, which is upregulated in adult worms, although they are under-represented in the secretome. The most abundant proteins in adult fluke secretions were helminth defense molecules that likely establish an immune environment permissive to fluke survival and/or neutralize pathogen-associated molecular patterns such as bacterial lipopolysaccharide in the microbiome-rich rumen. The distinct collection of molecules secreted by C. daubneyi allowed the development of the first coproantigen-based ELISA for paramphistomosis which, importantly, did not recognize antigens from other helminths commonly found as coinfections with rumen fluke.
Item Type: | Article |
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Uncontrolled Keywords: | Feces, Rumen, Animals, Cattle, Paramphistomatidae, Trematode Infections, Helminth Proteins, Antigens, Helminth, Life Cycle Stages, Cysteine Proteases, Transcriptome, Secretome |
Depositing User: | Symplectic Admin |
Date Deposited: | 26 Feb 2021 16:18 |
Last Modified: | 18 Jan 2023 22:58 |
DOI: | 10.1074/mcp.ra120.002175 |
Open Access URL: | https://doi.org/10.1074/mcp.RA120.002175 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3116126 |