Schistosoma mansoni immunomodulatory molecule Sm16/SPO-1/SmSLP is a member of the trematode-specific helminth defence molecules (HDMs).

Shiels, J; Cwiklinski, K; Alvarado, R; Thivierge, K; Cotton, S; Gonzales Santana, B; To, J; Donnelly, S; Taggart, CC; Weldon, S; Dalton, JP

Schistosoma mansoni immunomodulatory molecule Sm16/SPO-1/SmSLP is a member of the trematode-specific helminth defence molecules (HDMs).

Shiels, J Cwiklinski, K Alvarado, R Thivierge, K Cotton, S Gonzales Santana, B To, J

Donnelly, S

Taggart, CC Weldon, S Dalton, JP

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Publisher:: Public Library of Science (PLoS)
Publication Type:: Journal Article
Citation:: PLoS Negl Trop Dis, 2020, 14, (7), pp. e0008470
Issue Date:: 2020-07-09

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Field	Value	Language
dc.contributor.author	Shiels, J
dc.contributor.author	Cwiklinski, K
dc.contributor.author	Alvarado, R
dc.contributor.author	Thivierge, K
dc.contributor.author	Cotton, S
dc.contributor.author	Gonzales Santana, B
dc.contributor.author	To, J https://orcid.org/0000-0003-3482-4369
dc.contributor.author	Donnelly, S https://orcid.org/0000-0003-2005-3698
dc.contributor.author	Taggart, CC
dc.contributor.author	Weldon, S
dc.contributor.author	Dalton, JP
dc.date.accessioned	2020-07-14T20:40:16Z
dc.date.available	2020-06-10
dc.date.available	2020-07-14T20:40:16Z
dc.date.issued	2020-07-09
dc.identifier.citation	PLoS Negl Trop Dis, 2020, 14, (7), pp. e0008470
dc.identifier.issn	1935-2735
dc.identifier.uri	http://hdl.handle.net/10453/141778
dc.description.abstract	BACKGROUND: Sm16, also known as SPO-1 and SmSLP, is a low molecular weight protein (~16kDa) secreted by the digenean trematode parasite Schistosoma mansoni, one of the main causative agents of human schistosomiasis. The molecule is secreted from the acetabular gland of the cercariae during skin invasion and is believed to perform an immune-suppressive function to protect the invading parasite from innate immune cell attack. METHODOLOGY/PRINCIPAL FINDINGS: We show that Sm16 homologues of the Schistosomatoidea family are phylogenetically related to the helminth defence molecule (HDM) family of immunomodulatory peptides first described in Fasciola hepatica. Interrogation of 69 helminths genomes demonstrates that HDMs are exclusive to trematode species. Structural analyses of Sm16 shows that it consists predominantly of an amphipathic alpha-helix, much like other HDMs. In S. mansoni, Sm16 is highly expressed in the cercariae and eggs but not in adult worms, suggesting that the molecule is of importance not only during skin invasion but also in the pro-inflammatory response to eggs in the liver tissues. Recombinant Sm16 and a synthetic form, Sm16 (34-117), bind to macrophages and are internalised into the endosomal/lysosomal system. Sm16 (34-117) elicited a weak pro-inflammatory response in macrophages in vitro but also suppressed the production of bacterial lipopolysaccharide (LPS)-induced inflammatory cytokines. Evaluation of the transcriptome of human macrophages treated with a synthetic Sm16 (34-117) demonstrates that the peptide exerts significant immunomodulatory effects alone, as well as in the presence of LPS. Pathways most significantly influenced by Sm16 (34-117) were those involving transcription factors peroxisome proliferator-activated receptor (PPAR) and liver X receptors/retinoid X receptor (LXR/RXR) which are intricately involved in regulating the cellular metabolism of macrophages (fatty acid, cholesterol and glucose homeostasis) and are central to inflammatory responses. CONCLUSIONS/SIGNIFICANCE: These results offer new insights into the structure and function of a well-known immunomodulatory molecule, Sm16, and places it within a wider family of trematode-specific small molecule HDM immune-modulators with immuno-biotherapeutic possibilities.
dc.language	eng
dc.publisher	Public Library of Science (PLoS)
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1142006
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1142006
dc.relation	http://purl.org/au-research/grants/nhmrc/1142006
dc.relation.ispartof	PLoS Negl Trop Dis
dc.relation.isbasedon	10.1371/journal.pntd.0008470
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	06 Biological Sciences, 11 Medical and Health Sciences
dc.subject.classification	Tropical Medicine
dc.title	Schistosoma mansoni immunomodulatory molecule Sm16/SPO-1/SmSLP is a member of the trematode-specific helminth defence molecules (HDMs).
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	United States
utslib.for	06 Biological Sciences
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2020-07-14T20:40:06Z
pubs.issue	7
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	7

Abstract:

BACKGROUND: Sm16, also known as SPO-1 and SmSLP, is a low molecular weight protein (~16kDa) secreted by the digenean trematode parasite Schistosoma mansoni, one of the main causative agents of human schistosomiasis. The molecule is secreted from the acetabular gland of the cercariae during skin invasion and is believed to perform an immune-suppressive function to protect the invading parasite from innate immune cell attack. METHODOLOGY/PRINCIPAL FINDINGS: We show that Sm16 homologues of the Schistosomatoidea family are phylogenetically related to the helminth defence molecule (HDM) family of immunomodulatory peptides first described in Fasciola hepatica. Interrogation of 69 helminths genomes demonstrates that HDMs are exclusive to trematode species. Structural analyses of Sm16 shows that it consists predominantly of an amphipathic alpha-helix, much like other HDMs. In S. mansoni, Sm16 is highly expressed in the cercariae and eggs but not in adult worms, suggesting that the molecule is of importance not only during skin invasion but also in the pro-inflammatory response to eggs in the liver tissues. Recombinant Sm16 and a synthetic form, Sm16 (34-117), bind to macrophages and are internalised into the endosomal/lysosomal system. Sm16 (34-117) elicited a weak pro-inflammatory response in macrophages in vitro but also suppressed the production of bacterial lipopolysaccharide (LPS)-induced inflammatory cytokines. Evaluation of the transcriptome of human macrophages treated with a synthetic Sm16 (34-117) demonstrates that the peptide exerts significant immunomodulatory effects alone, as well as in the presence of LPS. Pathways most significantly influenced by Sm16 (34-117) were those involving transcription factors peroxisome proliferator-activated receptor (PPAR) and liver X receptors/retinoid X receptor (LXR/RXR) which are intricately involved in regulating the cellular metabolism of macrophages (fatty acid, cholesterol and glucose homeostasis) and are central to inflammatory responses. CONCLUSIONS/SIGNIFICANCE: These results offer new insights into the structure and function of a well-known immunomodulatory molecule, Sm16, and places it within a wider family of trematode-specific small molecule HDM immune-modulators with immuno-biotherapeutic possibilities.

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http://hdl.handle.net/10453/141778