Fasciola hepatica is refractory to complement killing by preventing attachment of mannose binding lectin (MBL) and inhibiting MBL-associated serine proteases (MASPs) with serpins

De Marco Verissimo, Carolina, Jewhurst, Heather L, Dobó, József, Gál, Péter, Dalton, John P and Cwiklinski, Krystyna ORCID: 0000-0001-5577-2735 (2022) Fasciola hepatica is refractory to complement killing by preventing attachment of mannose binding lectin (MBL) and inhibiting MBL-associated serine proteases (MASPs) with serpins. PLOS Pathogens, 18 (1). e1010226-e1010226.

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Official URL: http://dx.doi.org/10.1371/journal.ppat.1010226

Abstract

<jats:p>The complement system is a first-line innate host immune defence against invading pathogens. It is activated via three pathways, termed Classical, Lectin and Alternative, which are mediated by antibodies, carbohydrate arrays or microbial liposaccharides, respectively. The three complement pathways converge in the formation of C3-convertase followed by the assembly of a lethal pore-like structure, the membrane attack complex (MAC), on the pathogen surface. We found that the infectious stage of the helminth parasite <jats:italic>Fasciola hepatica</jats:italic>, the newly excysted juvenile (NEJ), is resistant to the damaging effects of complement. Despite being coated with mannosylated proteins, the main initiator of the Lectin pathway, the mannose binding lectin (MBL), does not bind to the surface of live NEJ. In addition, we found that recombinantly expressed serine protease inhibitors secreted by NEJ (rFhSrp1 and rFhSrp2) selectively prevent activation of the complement via the Lectin pathway. Our experiments demonstrate that rFhSrp1 and rFhSrp2 inhibit native and recombinant MBL-associated serine proteases (MASPs), impairing the primary step that mediates C3b and C4b deposition on the NEJ surface. Indeed, immunofluorescence studies show that MBL, C3b, C4b or MAC are not deposited on the surface of NEJ incubated in normal human serum. Taken together, our findings uncover new means by which a helminth parasite prevents the activation of the Lectin complement pathway to become refractory to killing <jats:italic>via</jats:italic> this host response, in spite of presenting an assortment of glycans on their surface.</jats:p>

Item Type:	Article
Uncontrolled Keywords:	Animals, Humans, Fasciola hepatica, Helminth Proteins, Mannose-Binding Lectin, Serpins, Complement System Proteins, Mannose-Binding Protein-Associated Serine Proteases, Immunity, Innate
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	24 Feb 2022 09:09
Last Modified:	18 Jan 2023 21:11
DOI:	10.1371/journal.ppat.1010226
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3149590