Mechanisms of immunomodulation by Brugia pahangi infective larvae and microfilariae

Osborne, Julie (1997) Mechanisms of immunomodulation by Brugia pahangi infective larvae and microfilariae. PhD thesis, University of Glasgow.

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Abstract

Lymphatic filariasis in humans is characterised by a profound bias in the immune response. Parasite specific Th1 responses, including proliferation, are dramatically impaired while Th2 responses predominate. In this study, a mouse model of filariasis was used to investigate the role of the infective form (the third stage larvae, L3) and the blood stage form (the microfilariae, mf) in modulating the immune response. Sub-cutaneous infection of BALB/c mice with L3 and mf of Brugia pahangi has a profound and contrasting effect on Th cell function, that appears to replicate, at least in part, the two striking aspects of the human immune response.

A Th2 response predominated and polyclonal Th1 responses and antigen-specific proliferation are down-regulated in L3-infected mice. Surprisingly, antigen-specific proliferation was absent in mf-infected mice in which a Th1-biased response dominated. Furthermore, after four days of culture in the presence of antigen spleen cells from mf-infected mice, but not L3-infected mice or uninfected controls, displayed a S.I<1. These data would suggest that spleen cells primed by infection with mf are undergoing accelerated death in culture. The remaining part of the study was focused on examining the mechanisms underlying the skewed responses in both L3- and mf-infected animals that may suggest some novel pathways operating in the infected human.

Treatment of spleen cells from L3-infected mice with neutralising anti-IL-4, anti-IL-10 or rIL-2 resulted in a dramatic increase in ConA-driven proliferation, IL-2 and IFN-gamma production. Interestingly, removal of the residuent spleen APC population and replacement with APC from uninfected animals also restored the defective mitogen-driven Th1 responses. Furthermore, replacing the APC population or neutralising IL-10, but not IL-4, resulted in antigen-specific IL-2 and IFN-gamma indicating that B. pahangi-primed Th1 cells do exist in L3-infected mice but appear to be unable to respond in the presence of IL-10 perhaps operating via its effect on APC function.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: S Agriculture > SF Animal culture > SF600 Veterinary Medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Funder's Name: UNSPECIFIED
Supervisor's Name: Devaney, Dr. Eileen
Date of Award: 1997
Depositing User: Ms Anikó Szilágyi
Unique ID: glathesis:1997-6492
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 16 Jun 2015 09:00
Last Modified: 16 Jun 2015 09:01
URI: http://theses.gla.ac.uk/id/eprint/6492

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