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Fasciola hepatica Tegumental antigen modulates macrophage phenotype and function

Adams, Paul (2013) Fasciola hepatica Tegumental antigen modulates macrophage phenotype and function. Master of Science thesis, Dublin City University.

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Abstract

Alternatively activated macrophages (M2) are antigen presenting cells that have a critical role in host tissue repair, regulation of host metabolism and modulation of adaptive immune responses. During helminth infection, they also act as powerful immune suppressors by suppressing Th1 immune responses. Fasciola hepatica infection drives a Th2 immune response, which is associated with the induction of M2 macrophages, in its mammalian host. The induction of Th2 immune responses and M2 macrophages can be mimicked by Fasciola excretory-secretory products (FhES). Here a second Fasciola antigen preparation consisting of the tegumental coat of F. hepatica was examined for its immune-modulatory properties on macrophages. In contrast to FhES, FhTeg does not induce antigen specific Th1 (IFN-γ) or Th2 (IL-4/IL-5/IL-13) cytokine responses during F. hepatica infection or following treatment intra-peritoneally with FhTeg.Despite the lack of Th2 cytokines, similar to FhES, FhTeg can modulate macrophages in vivo by inducing a M2-like phenotype that exhibited T-cell suppressive functional ability. This M2-like phenotype was largely STAT6 dependent and while FhTeg cannot induce Th2 specific adaptive immune responses it can induce IL-13 producing macrophages in vivo. FhTeg could not induce the M2-likemacrophages directly in vitro but rather indirectly through the stimulation of dendritic cells. M2 macrophages express c-type lectin receptors (CLR), a family of receptors that recognize specific pathogen-associated glycoconjugate structures. CLRs are involved in helminth antigen recognition, influencing immune responses associated with helminth infection. The CLRs, Mannose receptor and Macrophage Galactose Lectin were up-regulated during F. hepatica infection and this was mimicked by FhTeg in vivo and in vitro. This study was important because it helps us further understand the role FhTeg plays in F. hepatica host/parasite interactions.

Item Type:Thesis (Master of Science)
Date of Award:November 2013
Refereed:No
Supervisor(s):O'Neill, Sandra
Uncontrolled Keywords:Fasciola hepatica; Immune responses; Helminth infection; Immune suppressors
Subjects:Biological Sciences > Immunology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License
Funders:Programme for Research in Third Level Institutions (PRTLI) Cycle 4. The PRTLI is co-funded through the European Regional Development Fund (ERDF), part of the European Union Structural Funds Programme 2007-2013.
ID Code:19335
Deposited On:21 Nov 2013 14:46 by Sandra O'Neill. Last Modified 21 Nov 2013 14:46

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