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Title: Macroparasites, immune responses and immunoregulation in wild and laboratory murids
Author: Friberg, Ida Mari
ISNI:       0000 0004 2742 8285
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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This thesis primarily addresses environmental influences, in particular exposure to macroparasite infection, on immunoregulatory expression in wild and laboratory murid rodents. Experimental studies in laboratory mice demonstrated that Heligmosomoides bakeri infection was generally associated with upregulation of systemic toll-like receptor (TLR) expression and TLR-mediated cytokine production at times of peak standing worm burden. TLR function and patterns of expression of TLR and other immunoregulatory genes were also monitored in a time series of wild mice (Apodemus sylvaticus) from a natural population exposed to a range of macroparasites, including Heligmosomoides polygyrus. Differences between wild and laboratory mice in the pattern of coexpression of immunoregulatory and TLR genes and in the transcriptional responses of immunoregulatory genes to TLR-stimulation suggested a stronger regulatory bias in the wild compared to laboratory mice. Perhaps most strikingly, wild mice constitutively express relatively very much more TGF-Bl, TLR2 and TLR4, but not other immunoregulatory genes such as FoxP3, IL-l0 or TNF-a. This indicates that immunoregulatory differences between wild and laboratory mice may be linked to differences in TGF-B1 producing cells, rather than IL-10-producing or FoxP3+ cells. Immunoepidemiological analyses indicated a substantial association of macroparasitic infection (principally due to the louse Polyplax serrata and Heligmosomoides polygyrus) with TLR-mediated cytokine responsiveness in wild mice. Given the primary role of TLRs in anti-bacterial responses, the consistent experimental and epidemiological links between macroparasites and TLRs in this study are interpreted as a possible effect of exposure of the host to bacteria co-localizing in macroparasite infection foci. The identity of genes differentially upregulated in wild vs. laboratory mice might also relate to bacterial exposures (possibly influenced by macroparasite infection, given the associations with TLRs described above?). Thus, TLR2 and TLR4 are key innate anti- bacterial receptors and TGF-B1 is prominently secreted by Th3-type T-regulatory cells which are associated with mucosal tolerance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available