Infection by the helminth parasite Fasciola hepatica requires rapid regulation of metabolic, virulence, and invasive factors to adjust to its mammalian host

Krystyna Cwiklinski, Heather Jewhurst, Paul McVeigh, Tara Barbour, Aaron Maule, Jose F Tort, Sandra M O'Neill, Mark Robinson, Sheila M Donnelly, John Dalton

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)
352 Downloads (Pure)

Abstract

The parasite Fasciola hepatica infects a broad range of mammals with impunity. Following ingestion of parasites (metacercariae) by the host, newly excysted juveniles (NEJ) emerge from their cysts, rapidly penetrate the duodenal wall and migrate to the liver. Successful infection takes just a few hours and involves negotiating hurdles presented by host macromolecules, tissues and micro-environments, as well as the immune system. Here, transcriptome and proteome analysis of ex vivo F. hepatica metacercariae and NEJ reveal the rapidity and multitude of metabolic and developmental alterations that take place in order for the parasite to establish infection. We found that metacercariae despite being encased in a cyst are metabolically active, and primed for infection. Following excystment, NEJ expend vital energy stores and rapidly adjust their metabolic pathways to cope with their new and increasingly anaerobic environment. Temperature increases induce neoblast proliferation and the remarkable up-regulation of genes associated with growth and development. Cysteine proteases synthesised by gastrodermal cells are secreted to facilitate invasion and tissue degradation, and tegumental transporters, such as aquaporins, are varied to deal with osmotic/salinity changes. Major proteins of the total NEJ secretome include proteases, protease inhibitors and anti-oxidants, and an array of immunomodulators that likely disarm host innate immune effector cells. Thus, the challenges of infection by F. hepatica parasites are met by rapid metabolic and physiological adjustments that expedite tissue invasion and immune evasion; these changes facilitate parasite growth, development and maturation. Our molecular analysis of the critical processes involved in host invasion has identified key targets for future drug and vaccine strategies directed at preventing parasite infection.
Original languageEnglish
Pages (from-to)1-58
JournalMolecular & cellular proteomics : MCP
Volume17
Issue number4
Early online date10 Jan 2018
DOIs
Publication statusEarly online date - 10 Jan 2018

Fingerprint

Dive into the research topics of 'Infection by the helminth parasite Fasciola hepatica requires rapid regulation of metabolic, virulence, and invasive factors to adjust to its mammalian host'. Together they form a unique fingerprint.

Cite this