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Title: Alternatively activated macrophages recruited by Brugia malayi
Author: Loke, P.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The adult stage of the parasitic nematode Brugia malayi can live in the host lymphatics for many years and must have an extremely effective immuno-suppressive mechanism that prevents rejection. We have discovered that this parasite can induce alternatively activated IL-4 dependent macrophages that can block proliferation of other cells via a receptor-mediated mechanism. The proliferative block is reversible and is not a result of apoptosis. Furthermore, these suppressive cells can reduce the proliferation of a wide range of human cancer cell lines. These data demonstrates that B. malayi can lead to the activation of a novel mechanism of proliferative suppression, via IL-4 dependent macrophages. These macrophages may have important roles in altering host immune responses during parasitic infection and may even have the potential to reduce tumour cell growth. Another feature of B. malayi infection is a bias towards a type 2 immune response. To investigate the role that the B. malayi recruited antigen presenting cells have on naive T cells, the suppressive macrophages recruited by B. malayi was used to stimulate naive T cells from TCR transgenic mice. Although the naive T cells were inhibited by parasite-induced macrophages during primary stimulation, they proliferated normally upon secondary stimulation and were not rendered anergic. However, naive T cells primed by suppressive macrophages differentiated into IL-4 producing Th2 cells upon secondary stimulation instead of IFN-g producing Th1 cells, as has been previously described. Th2 differentiation was associated with the inhibition of (or failure or stimulate) IFN-g production during primary stimulation. Interestingly, blocking antibodies against TGF-b (but not IL-10) restored the differentiation of IFN-g producing Th1 cells. These data indicate that T cells exposed to parasite induced alternatively activated macrophages are driven towards Th2 differentiation. This may be an important factor in the Th2 bias that accompanies helminth infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available