A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis

Lund, Maria E., Greer, Judith M., Dixit, Aakanksha, Alvarado, Raquel, McCauley-Winter, Padraig, To, Joyce, Tanaka, Akane, Hutchinson, Andrew T., Robinson, Mark W., Simpson, Ann M., O'Brien, Bronwyn A., Dalton, John P. and Donnelly, Sheila (2016) A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis. Scientific Reports, 6 . doi:10.1038/srep37789


Author Lund, Maria E.
Greer, Judith M.
Dixit, Aakanksha
Alvarado, Raquel
McCauley-Winter, Padraig
To, Joyce
Tanaka, Akane
Hutchinson, Andrew T.
Robinson, Mark W.
Simpson, Ann M.
O'Brien, Bronwyn A.
Dalton, John P.
Donnelly, Sheila
Title A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-11-24
Year available 2016
Sub-type Article (original research)
DOI 10.1038/srep37789
Open Access Status DOI
Volume 6
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases.
Formatted abstract
Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases.
Keyword Autoimmunity
Parasite immune evasion
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID PP1758
1087341
322725
Institutional Status UQ
Additional Notes http:https://dx.doi.org/10.1038/srep37789

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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Created: Tue, 29 Nov 2016, 01:16:33 EST by Judith M Greer on behalf of UQ Centre for Clinical Research