Major secretory antigens of the Helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses

Dowling, DJ; Hamilton, CM; Donnelly, S; La Course, J; Brophy, PM; Dalton, J; O'Neill, SM

Major secretory antigens of the Helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses

Dowling, DJ Hamilton, CM Donnelly, S

La Course, J Brophy, PM Dalton, J O'Neill, SM

Permalink

Publication Type:: Journal Article
Citation:: Infection and Immunity, 2010, 78 (2), pp. 793 - 801
Issue Date:: 2010-02-01

Closed Access

	Filename	Description	Size
	2011001721OK.pdf		1.63 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Dowling, DJ	en_US
dc.contributor.author	Hamilton, CM	en_US
dc.contributor.author	Donnelly, S https://orcid.org/0000-0003-2005-3698	en_US
dc.contributor.author	La Course, J	en_US
dc.contributor.author	Brophy, PM	en_US
dc.contributor.author	Dalton, J	en_US
dc.contributor.author	O'Neill, SM	en_US
dc.date.issued	2010-02-01	en_US
dc.identifier.citation	Infection and Immunity, 2010, 78 (2), pp. 793 - 801	en_US
dc.identifier.issn	0019-9567	en_US
dc.identifier.uri	http://hdl.handle.net/10453/17380
dc.description.abstract	Fasciola hepatica is a helminth pathogen that drives Th2/Treg immune responses in its mammalian host. The parasite releases a large number of molecules that are critical to inducing this type of immune response. Here we have selected recombinant forms of two major F. hepatica secreted molecules, the protease cathepsin L (rFhCL1) and an antioxidant, sigma class glutathione transferase (rFhGST-si), to examine their interactions with dendritic cells (DCs). Despite enzymatic and functional differences between these molecules, both induced interleukin-6 (IL-6), IL-12p40, and macrophage inflammatory protein 2 (MIP-2) secretion from DCs and enhanced CD40 expression. While this induction was mediated by Toll-like receptor 4 (TLR4), the subsequent intracellular signaling pathways differed; rFhCL1 signaled through p38, and rFhGST-si mediated its effect via c-Jun N-terminal kinase (JNK), p38, p-NF-κBp65, and IRF5. Neither rFhCL1 nor rFhGST-si enhanced DC phagocytosis or induced Th2 immune responses in vivo. However, DCs matured in the presence of either enzyme attenuated IL-17 production from OVA peptide-specific T cells in vivo. In addition, DCs exposed to either antigen secreted reduced levels of IL-23. Therefore, both F. hepatica FhCL1 and FhGST-si modulate host immunity by suppressing responses associated with chronic inflammation-an immune modulatory mechanism that may benefit the parasite's survival within the host. Copyright © 2010, American Society for Microbiology. All Rights Reserved.	en_US
dc.relation.ispartof	Infection and Immunity	en_US
dc.relation.isbasedon	10.1128/IAI.00573-09	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Dendritic Cells	en_US
dc.subject.mesh	T-Lymphocyte Subsets	en_US
dc.subject.mesh	Th1 Cells	en_US
dc.subject.mesh	Th2 Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Fasciola hepatica	en_US
dc.subject.mesh	Fascioliasis	en_US
dc.subject.mesh	Interleukin-17	en_US
dc.subject.mesh	Antigens, Helminth	en_US
dc.subject.mesh	Blotting, Western	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Phenotype	en_US
dc.title	Major secretory antigens of the Helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	78	en_US
utslib.for	1107 Immunology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	07 Agricultural and Veterinary Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
dc.location.activity	United States
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	78	en_US

Abstract:

Fasciola hepatica is a helminth pathogen that drives Th2/Treg immune responses in its mammalian host. The parasite releases a large number of molecules that are critical to inducing this type of immune response. Here we have selected recombinant forms of two major F. hepatica secreted molecules, the protease cathepsin L (rFhCL1) and an antioxidant, sigma class glutathione transferase (rFhGST-si), to examine their interactions with dendritic cells (DCs). Despite enzymatic and functional differences between these molecules, both induced interleukin-6 (IL-6), IL-12p40, and macrophage inflammatory protein 2 (MIP-2) secretion from DCs and enhanced CD40 expression. While this induction was mediated by Toll-like receptor 4 (TLR4), the subsequent intracellular signaling pathways differed; rFhCL1 signaled through p38, and rFhGST-si mediated its effect via c-Jun N-terminal kinase (JNK), p38, p-NF-κBp65, and IRF5. Neither rFhCL1 nor rFhGST-si enhanced DC phagocytosis or induced Th2 immune responses in vivo. However, DCs matured in the presence of either enzyme attenuated IL-17 production from OVA peptide-specific T cells in vivo. In addition, DCs exposed to either antigen secreted reduced levels of IL-23. Therefore, both F. hepatica FhCL1 and FhGST-si modulate host immunity by suppressing responses associated with chronic inflammation-an immune modulatory mechanism that may benefit the parasite's survival within the host. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/17380